A prospective study of the serum prostate specific antigen concentrations and Gleason histologic scores of black and white men with prostate carcinoma.

BACKGROUND: The stage specific survival rates of black American men with prostate carcinoma are less favorable than those of white American men. The authors conducted a prospective study of the serum prostate specific antigen (PSA) concentrations and Gleason histologic scores of black and white men with newly diagnosed prostate carcinoma to determine whether there were racial differences in these prognostic variables. METHODS: At a Veterans Affairs Medical Center between January 1, 1992, and December 31, 1997, clinical stage, Gleason histologic score, serum PSA concentration, prostate volume, and PSA density were determined for 796 consecutive men (465 black and 331 white) who had biopsy-detected prostate carcinoma. RESULTS: The percentages, respectively, of black and white men with local, regional, and metastatic carcinoma were 58 and 72; 22 and 17; and 20 and 11 (P < 0.0001). Of 271 black and 329 white men with local stage cancer, 20% and 12%, respectively, had Gleason 8-10 tumors (P = 0.02), and the age-adjusted risk of Gleason 8-10 cancer was 1.39 times greater for black men (95% confidence interval [CI] = 1.09-2.93). Gleason 8-10 cancer was found in 12 of 68 black (18%) and 5 of 87 white (6%) men with local cancer who were age 65 years or younger (P = 0.02). Among black and white men with local stage cancer, the mean PSA was 12.9 (95% CI = 11.5-14.4) and 8.5 (95% CI = 7.6-9.4) ng/mL, respectively (P < 0.0001), and among black and white men with regional stage cancer the mean PSA was 53.3 (95% CI = 42.7-63.9) and 35.0 (95% CI = 27.3-42.6) ng/mL, respectively (P = 0.02). The mean PSA of black and white men with local cancer who were age 65 years or younger was 11.6 (95% CI = 8.8-14.4) and 6.9 (95% CI = 5.9-8.0) ng/mL, respectively (P = 0.0009). CONCLUSIONS: Disparities in the risk of Gleason score 8-10 cancer for black and white men with local stage disease and in the serum PSA concentrations of black and white men with local and regional stage disease help to explain racial differences in cancer survival. Racial differences in the risk of Gleason 8-10 cancer and in the serum PSA concentrations of men age 65 years or younger have implications regarding the potential benefits of screening for prostate carcinoma in the African American community.     

Prostate-specific antigen velocity and the detection of gleason score 7 to 10 prostate cancer

BACKGROUND: An increasing prostate-specific antigen (PSA) velocity is associated with a shorter survival after local therapy for prostate cancer. In this study, the authors evaluated whether PSA velocity was associated with prostate cancer detection and grade at diagnosis after adjusting for established predictors. METHODS: Between January 1989 and December 2003, 914 men who had PSA levels >/=4 ng/mL were identified by using the Center for Prostate Disease Research (CPDR) multicenter national database, including 541 men who were diagnosed with prostate cancer. Multivariable logistic regression analyses were performed that included continuous variables (PSA velocity and level, number of prior negative biopsies, and age) along with categorical variables (ethnicity and family history) were used to identify the factors associated with prostate cancer detection and grade. RESULTS: An increasing PSA velocity was associated with Gleason scores from 7 to 10 versus Gleason scores form 2 to 6 or no cancer (adjusted odds ratio [OR], 1.04 ng/mL per year; 95% confidence interval [95% CI], 1.003-1.085 ng/mL per year; P = .035). This finding was not evident in patients who had prostate cancers with Gleason scores between 2 and 6 or for any prostate cancer. PSA level was associated with the detection of any prostate cancer (OR, 1.06 ng/mL; 95% CI, 1.03-1.10 ng/mL; P = .004) and Gleason score 4 ng/mL. These findings, in conjunction with life expectancy, may be used when deciding which men should not be recommended for prostate biopsy despite a PSA level >4 ng/mL.     

Prostate-specific antigen testing of older men.

BACKGROUND: Elevated serum prostate-specific antigen (PSA) levels are predictive of a future diagnosis of prostate cancer. To test the hypothesis that older men with low PSA levels may require less intensive PSA testing because of a reduced prostate cancer detection rate, we evaluated the association between age, baseline PSA level, and prostate cancer detection. METHODS: We conducted a prospective cohort study among participants in a study of aging who had serial PSA measurements taken from age 60 or 65 years until they either were diagnosed with prostate cancer (cancer case subjects) or reached the age of 75 years (subjects without prostate cancer). The time of cancer detection among cancer case subjects was defined as the measurement date on which a PSA level above 4.0 ng/mL was detected (i.e., PSA conversion). Cancer case subjects and subjects without prostate cancer were analyzed according to baseline PSA level and age. RESULTS: All cancer case subjects in the 60-year-old cohort had baseline PSA levels above 0.5 ng/mL, and 14 of 15 cancer cases that would have been detected by a PSA conversion among the 65-year-old cohort were associated with baseline PSA levels of 1.1 ng/mL or more. If PSA testing were discontinued in men aged 65 years with PSA levels of 0.5 ng/mL or less, 100% (95% confidence interval [CI] = 78%-100%) of the cancers would still be detected by age 75 years; if PSA testing were discontinued in men aged 65 years who had PSA levels of 1.0 ng/mL or less, 94% (95% CI = 70%-100%) of the cancers would still be detected by age 75 years. CONCLUSIONS: These data suggest that a decrease in the intensity of screening among older men with low PSA values may not lead to an increase in undetected prostate cancer.     

Prospective study of cancer detection in black and white men with normal digital rectal examination but prostate specific antigen equal or greater than 4.0 ng/mL

BACKGROUND: The serum prostate specific antigen (PSA) concentration with no clinical evidence of prostate carcinoma is higher and more variable in black than in white American men. The influence of this phenomenon on relations between race, PSA, and cancer detection in men with a PSA greater than or equal to 4.0 ng/mL has not been investigated. METHODS: Between January 1992 and December 2000, 451 black and 480 white men with a normal digital rectal examination and a PSA greater than or equal to 4.0 ng/mL had an initial prostate biopsy at one medical center. The histology of the biopsy specimens and the Gleason score of malignant specimens was determined by one uropathologist. RESULTS: Cancer was detected in 207 (46%) black and 167 (35%) white men (P = 0.0006). When adjusted for PSA, cancer detection was also greater in the black than the white men, but the difference did not achieve statistical significance (relative risk, 1.30; 95% confidence interval [CI], 0.99-1.71; P = 0.06). Gleason score 7-10 cancer was detected in 88 (20%) black and 45 (9%) white men (P = 0.0001), and the difference remained significant when adjusted for PSA (relative risk, 1.73; 95% CI, 1.16-2.61; P = 0.0008). In the intermediate PSA range of 4.0-9.9 ng/mL, cancer detection and Gleason score 7-10 cancer detection was greater in black than in white men younger than 60, 60-69, and 70 years of age or older, but the difference was significant only for Gleason score 7-10 cancer detection among men 60-69 years of age (P = 0.006). CONCLUSIONS: There is a direct correlation between Gleason score and cause specific survival with local stage prostate carcinoma. The authors' study indicates that prostate carcinomas with established malignant potential are more likely to be identified in black than in white men with PSA elevation as the only indication of malignancy and raises the possibility that a PSA threshold less than 4.0 ng/mL in black men younger than 70 years of age may reduce racial disparities in prostate carcinoma morbidity and mortality.     

Prostate-specific antigen velocity and prostate cancer gleason grade and stage

BACKGROUND: Increased preoperative prostate-specific antigen (PSA) velocity (PSAV) has been associated with increased prostate cancer mortality and higher Gleason scores. The authors evaluated the relation between PSAV, biopsy Gleason score, and pathologic stage in men who were enrolled in a prostate cancer screening trial. METHODS: Data were analyzed from 1441 men who were enrolled in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial who received > or =2 PSA screens and were diagnosed with prostate cancer within 1 year of the last screen. PSAV was estimated by using all screening PSA values within 6 years prediagnosis. RESULTS: Both PSA and PSAV were related to biopsy Gleason score. The multivariable odds ratios (OR), controlling for PSA and demographics, for having a Gleason score of 7 to 10 were 1.3 (95% confidence interval [95% CI], 0.9-1.9), 2.2 (95% CI, 1.5-3.3), and 2.3 (95% CI, 1.4-3.9) for men with PSAV values from 0.5 to 1 ng/mL per year, from 1 to 2 ng/mL per year, and >2 ng/mL per year, respectively, compared with men who had PSAV values <0.5 ng/mL per year. The median PSAV was 0.60 ng/mL per year for men with Gleason scores from 2 to 6 versus 0.84 ng/mL per year for men with Gleason scores from 7 to 10 (P < .0001). Among 658 men who underwent prostatectomy, both PSA and PSAV were associated with advanced pathologic stage in univariate analyses; however, when the analysis controlled for clinical stage and biopsy Gleason score, the associations of PSA and PSAV were no longer statistically significant. CONCLUSIONS: PSAV and PSA levels were associated independently with biopsy Gleason score. Among men who underwent prostatectomy, PSAV and PSA were not predictive of advanced pathologic stage when the analysis was controlled for biopsy Gleason score and clinical stage. It cannot be determined yet whether PSAV is predictive of long-term prostate cancer outcome in this cohort.     

Oxidative DNA damage in prostate cancer patients consuming tomato sauce-based entrees as a whole-food intervention.

BACKGROUND: Human prostate tissues are vulnerable to oxidative DNA damage. The risk of prostate cancer is lower in men reporting higher consumption of tomato products, which contain high levels of the antioxidant lycopene. We examined the effects of consumption of tomato sauce-based pasta dishes on lycopene uptake, oxidative DNA damage, and prostate-specific antigen (PSA) levels in patients already diagnosed with prostate cancer. METHODS: Thirty-two patients with localized prostate adenocarcinoma consumed tomato sauce-based pasta dishes for the 3 weeks (30 mg of lycopene per day) preceding their scheduled radical prostatectomy. Serum and prostate lycopene concentrations, serum PSA levels, and leukocyte DNA oxidative damage (ratio of 8-hydroxy-2'-deoxyguanosine [8-OHdG] to 2'-deoxyguanosine [dG]) were assessed before and after the dietary intervention. DNA oxidative damage was assessed in resected prostate tissue from study participants and from seven randomly selected prostate cancer patients. All statistical tests were two-sided. RESULTS: After the dietary intervention, serum and prostate lycopene concentrations were statistically significantly increased, from 638 nM (95% confidence interval [CI] = 512 to 764 nM) to 1258 nM (95% CI = 1061 to 1455 nM) (P<.001) and from 0.28 nmol/g (95% CI = 0.18 to 0.37 nmol/g) to 0.82 nmol/g (95% CI = 0.57 to 1.11 nmol/g) (P <.001), respectively. Compared with preintervention levels, leukocyte oxidative DNA damage was statistically significantly reduced after the intervention, from 0.61 8-OHdG/10(5) dG (95% CI = 0.45 to 0.77 8-OHdG/10(5) dG) to 0.48 8-OHdG/ 10(5) dG (95% CI = 0.41 to 0.56 8-OHdG/10(5) dG) (P =.005). Furthermore, prostate tissue oxidative DNA damage was also statistically significantly lower in men who had the intervention (0.76 8-OHdG/10(5) dG [95% CI = 0.55 to 0.96 8-OHdG/10(5) dG]) than in the randomly selected patients (1.06 8-OHdG/10(5) dG [95% CI = 0.62 to 1.51 8-OHdG/10(5) dG]; P =.03). Serum PSA levels decreased after the intervention, from 10.9 ng/mL (95% CI = 8.7 to 13.2 ng/mL) to 8.7 ng/mL (95% CI = 6.8 to 10.6 ng/mL) (P<.001). CONCLUSION: These data indicate a possible role for a tomato sauce constituent, possibly lycopene, in the treatment of prostate cancer and warrant further testing with a larger sample of patients, including a control group.     

Preoperative serum caveolin-1 as a prognostic marker for recurrence in a radical prostatectomy cohort.

PURPOSE: Up-regulation of caveolin-1 (cav-1) is associated with virulent prostate cancer, and serum cav-1 levels are elevated in prostate cancer patients but not in benign prostatic hyperplasia. In this study, we evaluated the potential of high preoperative serum cav-1 levels to predict biochemical progression of prostate cancer. The value of the combined preoperative markers, prostate-specific antigen (PSA), biopsy Gleason score, and serum cav-1 for predicting biochemical recurrence was also investigated. EXPERIMENTAL DESIGN: Serum samples taken from 419 prostate cancer patients before radical prostatectomy were selected from our Specialized Programs of Research Excellence prostate cancer serum and tissue bank. Serum samples were obtained 0 to 180 days before surgery and all patients had complete data on age, sex, race, stage at enrollment, and follow-up for biochemical recurrence. Serum cav-1 levels were measured according to our previously reported ELISA protocol. RESULTS: Cav-1 levels were measured in the sera of 419 prostate cancer patients; the mean serum level was 4.52 ng/mL (median 1.01 ng/mL). Patients with high serum cav-1 levels had a 2.7-fold (P = 0.0493) greater risk of developing biochemical recurrence compared with those with low serum cav-1 levels. Importantly, patients with serum PSA >/= 10 ng/mL and elevated levels of serum cav-1 had 2.44 times higher risk (P = 0.0256) of developing biochemical recurrence compared with patients with low levels of cav-1. In addition, high serum cav-1 levels combined with increasing biopsy Gleason score predicted much shorter recurrence-free survival in the group of patients with PSA >/= 10 ng/mL (P = 0.0353). Cav-1 was also able to distinguish between high- and low- risk patients with biopsy Gleason score of seven, after adjusting, for patients PSA levels (P = 0.0429). CONCLUSIONS: Overall, elevated preoperative levels of serum cav-1 predict decreased time to cancer recurrence. In the subset of patients with serum PSA of >/=10 ng/mL, the combination of serum cav-1 and biopsy Gleason score has the capacity to predict time to biochemical recurrence.     

Predictors of mortality after androgen-deprivation therapy in patients with rapidly rising prostate-specific antigen levels after local therapy for prostate cancer

BACKGROUND: The authors identified biochemical and pathologic factors that were associated significantly with prostate cancer-specific mortality (PCSM) after androgen deprivation therapy (ADT) in men who had rapidly rising prostate-specific antigen (PSA) levels after they received local treatment. METHODS: The study population consisted of 67 patients who had a PSA doubling time (DT) < or =6 months after radical prostatectomy (n = 50 patients) or external beam radiation therapy (n = 17 patients) for localized prostate cancer. Multivariate Cox proportional hazards regression analysis was used to evaluate whether the interval to PSA failure, pre-ADT PSA DT, PSA level at the time of ADT initiation, time to PSA nadir, PSA nadir after 8 months on ADT, and Gleason score were associated significantly with the time to PCSM 8 months after the initiation of ADT. RESULTS.: A PSA nadir >0.2 ng/mL (adjusted hazard ratio [HR], 8.0; 95% confidence interval [95% CI], 1.7-38.7; P = 0.009) and a Gleason score > or =8 (adjusted HR, 5.2; 95% CI, 1.3-20.6; P = 0.02) were associated significantly with a short time to PCSM. The cumulative incidence estimates of 3-year PCSM were 5.8% versus 50.9% for patients with a PSA nadir < or =0.2 ng/mL versus >0.2 ng/mL, respectively, and 10.8% versus 35.8% for patients who had tumors with a Gleason score < or =7 versus > or =8, respectively. CONCLUSIONS.: Among men with a PSA DT < or =6 months, both a PSA nadir >0.2 ng/mL after ADT and a Gleason score > or =8 cancer identified men who were at high risk for PCSM. These men would be ideal candidates for Phase III studies that evaluate the impact on survival of new systemic therapies for prostate cancer.     

前列腺癌患者全血锌浓度的改变及诊断价值

目的:研究全血锌浓度与前列腺癌的关系,并将其与血清前列腺特异性抗原(PSA)联合,探讨在前列腺癌诊断中的应用价值.方法:收集自2005年7月至2008年10月东南大学附属中大医院和南京大学医学院附属鼓楼医院收治的前列腺癌患者95例,前列腺增生症患者91例,采用火焰吸收原子分光光度法测定全血锌浓度,采用放射免疫法测定血清PSA值.结果:全血锌浓度前列腺癌组(4.73±1.51)μg/mL,前列腺增生症组(6.82±1.63)μg/mL,两组间有显著差异(P＜0.001).两组血清PSA值总体分布有显著差异(P＜0.01),但在4.0～10.0ng/mL区间,两组例数比例无显著差异(P=0.143).以前列腺增生症组为对照,全血锌浓度诊断前列腺癌的ROC曲线下面积为0.82;在血清PSA4.0～10.0ng/mL区间范围,此曲线下面积为0.79.在血清PSA4.0～10.0ng/mL区间范围,全血锌浓度取5.24μg/mL界值时有最佳的诊断准确性,Youden指数0.46;其与血清PSA取界值4.0ng/mL串联应用,诊断的特异度为75%,是血清PSA单独诊断时的2.34倍,Youden指数为0.51,是血清PSA单独诊断的2.22倍,并联无助于诊断,Youden指数仅0.14.结论:全血锌浓度检测有助于前列腺癌与前列腺增生症的鉴别诊断,其与血清PSA联合应用(串联),能够显著改善血清PSA 4.0～10.0ng/mL区间内的诊断阳性率,可为前列腺癌的诊断提供有价值的参考,有一定的临床应用前景.     

Impact of age, benign prostatic hyperplasia, and cancer on prostate-specific antigen level

BACKGROUND: The distribution of prostate-specific antigen (PSA) values for men with or without prostate carcinoma are confounded because of verification bias. Correcting for verification bias, the means and variances of PSA values were estimated in specific clinical scenarios. METHODS: Existing receiver operating characteristic (ROC) curves, adjusted for the presence of verification bias in a screening population, were used to estimate the mean and variance of PSA values for men with or without prostate carcinoma, stratified by age and the presence or absence of benign prostatic hyperplasia. Men with a suspicious digital rectal exam (nodular) were excluded from analysis. RESULTS: Among men with cancer and the absence of benign prostatic hyperplasia, mean PSA values were 2.05 ng/mL and 2.66 ng/mL for younger (<60 yr) and older (> or =60 yrs) men, respectively. These estimates were 2.56 ng/mL and 3.90 ng/mL in the presence of benign prostatic hyperplasia for younger and older men, respectively. For men without prostate carcinoma, these values were 0.78 ng/mL and 1.23 ng/mL for younger and older men, respectively, among those without benign prostatic hyperplasia, and 0.97 ng/mL and 1.75 ng/mL for younger and older men, respectively, among those with benign prostatic hyperplasia. CONCLUSIONS: Accurate estimates of the mean and variance of PSA values for men with or without cancer may provide PSA thresholds for biopsy that are specific for age and prostate size as assessed by digital rectal exam. Therefore, the current threshold of 4.0 ng/mL should not be applied indiscriminately.     

Percent free prostate-specific antigen (PSA) is an accurate predictor of prostate cancer risk in men with serum PSA 2.5 ng/mL and lower

BACKGROUND: Up to 17% of men with a prostate-specific antigen (PSA) level below the accepted prostate biopsy cutoff of 2.5 ng/mL may have prostate cancer. Because identification of these patients represents a difficult task, we assessed the ability of percent free PSA to discriminate between benign and malignant prostate biopsy outcomes in men with PSA < or =2.5 ng/mL. METHODS: Between 1999 and 2006, 543 men with a PSA < or =2.5 ng/mL were referred for initial prostate biopsy. Age, total PSA, percent free PSA, and digital rectal examination findings represented predictors of prostate cancer at biopsy in logistic regression models. The area under the receiver operating characteristics curve (AUC) quantified the discriminative ability of the predictors. The pathological characteristics of the detected cancers were assessed in individuals treated with radical prostatectomy. RESULTS: Of all, 23% had prostate cancer on biopsy, 16.5% of patients treated with radical prostatectomy had pT3 stage, and 35.6% had a pathological Gleason score of 3 + 4 or higher. The most accurate predictor of prostate cancer on biopsy was percent free PSA (0.68) versus age (0.50), total PSA (0.57), or rectal examination findings (0.58). Of patients with percent free PSA below 14%, 59% had prostate cancer. In multivariate models, percent free PSA (P < .001) and rectal examination findings (P = .001) were the only independent predictors of prostate cancer. The combined AUC of all predictors (0.69) was not significantly (P = .7) higher than that of percentage of free PSA alone (0.68). CONCLUSIONS: The risk of prostate cancer is clearly non-negligible in patients with PSA < or =2.5 ng/mL. The percent free PSA can accurately predict the prevalence of prostate cancer at prostate biopsy in these individuals.     

Plasma insulin-like growth factor-I, insulin-like growth factor-binding proteins, and prostate cancer risk: a prospective study

BACKGROUND: Recent studies have suggested that men with elevated plasma levels of insulin-like growth factor-I (IGF-I) may have an increased risk of prostate cancer. Furthermore, IGF-binding proteins (IGFBPs) and insulin can modulate the activity of IGF-I. In this study, we sought to determine the role of IGF-I as well as IGFBPs-1, -2, and -3 and insulin as possible etiologic factors for prostate cancer. METHODS: We conducted a nested case-control study within the Northern Sweden Health and Disease Cohort Study. We measured levels of IGF-I, IGFBP-1, IGFBP-2, IGFBP-3, and insulin in plasma samples from 149 men who had a diagnosis of prostate cancer between 1 month and 10 years after blood collection and among 298 control men. All statistical tests are two-sided. RESULTS: Case subjects had statistically significantly higher mean levels of IGF-I than control subjects (229 ng/mL; 95% confidence interval [CI] = 218-240 ng/mL] versus 214 ng/mL [95% CI = 208-221 ng/mL]; P =.02) and IGFBP-3 (2611 ng/mL [95% CI = 2518-2704 ng/mL] versus 2498 ng/mL [95% CI = 2437-2560 ng/mL]; P =.04). Conditional logistic regression analyses showed increases in prostate cancer risk with rising levels of IGF-I (P:(for trend) =.02) and IGFBP-3 (P(for trend) =.03). In case subjects younger than 59 years at the time of blood collection, the risk associated with increased IGF-I was higher (P:(for trend) =.01), whereas the risk associated with increased IGFBP-3 was lower (P(for trend) =.44) than the corresponding risks in the full cohort. Prostate cancer risk was not associated with levels of IGFBP-1, IGFBP-2, or insulin. CONCLUSIONS: Prostate cancer risk is increased in men with elevated plasma IGF-I. This association was particularly strong in younger men in this study, suggesting that circulating IGF-I may be specifically involved in the early pathogenesis of prostate cancer.     

Antioxidant vitamin and mineral supplementation and prostate cancer prevention in the SU.VI.MAX trial

Randomized trials have shown, unexpectedly, that supplementation with selenium or vitamin E is associated with a reduction of prostate cancer risk. We assess whether a supplementation with low doses of antioxidant vitamins and minerals could reduce the occurrence of prostate cancer and influence biochemical markers. The SU.VI.MAX trial comprised 5,141 men randomized to take either a placebo or a supplementation with nutritional doses of vitamin C, vitamin E, beta-carotene, selenium and zinc daily for 8 years. Biochemical markers of prostate cancer risk such as prostate-specific antigen (PSA) and insulin-like growth factors (IGFs) were measured on plasma samples collected at enrollment and at the end of follow-up from 3,616 men. Cox regression models were used to estimate the hazard ratio and related 95% confidence interval of prostate cancer associated with the supplementation and to examine whether the effect differed among predetermined susceptible subgroups. During the follow-up, 103 cases of prostate cancer were diagnosed. Overall, there was a moderate nonsignificant reduction in prostate cancer rate associated with the supplementation (hazard ratio = 0.88; 95% CI = 0.60-1.29). However, the effect differed significantly between men with normal baseline PSA (< 3 microg/L) and those with elevated PSA (p = 0.009). Among men with normal PSA, there was a marked statistically significant reduction in the rate of prostate cancer for men receiving the supplements (hazard ratio = 0.52; 95% CI = 0.29-0.92). In men with elevated PSA at baseline, the supplementation was associated with an increased incidence of prostate cancer of borderline statistical significance (hazard ratio = 1.54; 95% CI = 0.87-2.72). The supplementation had no effect on PSA or IGF levels. Our findings support the hypothesis that chemoprevention of prostate cancer can be achieved with nutritional doses of antioxidant vitamins and minerals.     

A case-cohort study of human herpesvirus 8 seropositivity and incident prostate cancer in Tobago

Background

We previously reported a cross-sectional association between the presence of human herpesvirus 8 (HHV-8) serum antibodies and screen-detected prostate cancer in men living in Tobago. In the same study population, we examined the association between HHV-8 seropositivity and incident prostate cancer discovered at later screenings.

Methods

In 40-81 year-old men without prostate cancer discovered at initial digital rectal examination (DRE) and prostate-specific antigen (PSA) screening, a case-cohort design measured the association between baseline HHV-8 seropositivity (modified immunofluorescence assay for antibodies against HHV-8 lytic antigens) and incident prostate cancer detected at DRE and PSA screenings three or five years later.

Results

Analyses included 486 unique individuals, 96 incident prostate cancer cases, and 415 randomly selected subjects representing an at-risk cohort. By design, the random sub-cohort contained 25 incident prostate cancer cases. In the sub-cohort, the frequency of HHV-8 seropositivity increased across age groupings (40-49 years: 3.5%, 50-59 years: 13.6%, and ≥ 60 years: 22.9%). HHV-8 seropositivity was higher in men with elevated (≥ 4.0 ng/mL) than men with non-elevated PSA at initial screening (30.4% vs. 9.9% seropositive; crude odds ratio (OR) 3.96, 95% confidence interval (CI) 1.53-10.2; age-adjusted OR 2.42, 95% CI 0.91-6.47). HHV-8 seropositivity did not increase incident prostate cancer risk (age-adjusted hazard ratio (HR) 0.88, 95% CI 0.46-1.69).

Conclusions

Case-cohort analysis did not identify association between HHV-8 seropositivity and incident prostate cancer. However, analyses uncovered possible association between HHV-8 and PSA (a marker of prostate inflammation). Co-occurrence of HHV-8 seropositivity and PSA elevation may explain cross-sectional association between HHV-8 and PSA screen-detected prostate cancer.     

African-American men with nonpalpable prostate cancer exhibit greater tumor volume than matched white men

BACKGROUND: Although prostate cancer (PC) mortality disproportionately affects African-American (AA) men, limited data exist comparing the pathologic characteristics of white and AA patients with nonpalpable PC (clinical stage T1c). METHODS: The authors reviewed the radical prostatectomy (RP) specimens from 37 consecutive AA men with clinical stage T1c PC and 35 white men who were matched for age, clinical stage, serum prostate-specific antigen (PSA) level, year of surgery, prostate weight, and prostate biopsy strategy. Pathologic characteristics were compared after mapping tumor foci and calculating tumor volumes by using computer software. RESULTS: For AA men, the median age (57.7 years), mean serum PSA level (9.3 ng/mL), mean prostate weight (43 g), and biopsy strategy (73% sextant) were matched with the cohort of 35 white men (median age, 57.1 years; mean PSA, 9.3 ng/mL;, mean prostate weight, 43 g; biopsy strategy, 66% sextant). Despite similar biopsy characteristics between the 2 groups (Gleason score > or =7 in 43% of AA men vs. 37% of white men), AA men exhibited significantly higher prostatectomy Gleason scores (> or =7 in 76% of AA men vs. 34% of white men; P = .01). AA men also had a higher mean tumor volume (1.82 cm3 vs. 0.72 cm3; P = .001) and had 2.8 times more tumor per ng/mL of serum PSA (0.22 cm3 per ng/mL vs. 0.079 cm3 per ng/mL; P = .001). CONCLUSIONS: Compared with a cohort of white men with similar clinical features at the time of biopsy, AA men with nonpalpable PC had higher prostatectomy Gleason scores, greater cancer volume, and greater tumor volume per ng/mL of serum PSA. These data provide additional support for the concept of early PC detection using a serum PSA threshold of 2.5 ng/mL for biopsy among AA men.     

Biochemical outcome after radical prostatectomy or external beam radiation therapy for patients with clinically localized prostate carcinoma in the prostate specific antigen era

BACKGROUND: To the authors' knowledge, consensus is lacking regarding the relative long-term efficacy of radical prostatectomy (RP) versus conventional-dose external beam radiation therapy (RT) in the treatment of patients with clinically localized prostate carcinoma. METHODS: A retrospective cohort study of 2635 men treated with RP (n = 2254) or conventional-dose RT (n = 381) between 1988-2000 was performed. The primary endpoint was prostate specific antigen (PSA) survival stratified by treatment received and high-risk, intermediate-risk, or low-risk group based on the serum PSA level, biopsy Gleason score, 1992 American Joint Commission on Cancer clinical tumor category, and percent positive prostate biopsies. RESULTS: Estimates of 8-year PSA survival (95% confidence interval [95% CI]) for low-risk patients (T1c,T2a, a PSA level < or = 10 ng/mL, and a Gleason score < or = 6) were 88% (95% CI, 85, 90) versus 78% (95% CI, 72, 83) for RP versus patients treated with RT, respectively. Eight-year estimates of PSA survival also favored RP for intermediate-risk patients (T2b or Gleason score 7 or a PSA level > 10 and < or = 20 ng/mL) with < 34% positive prostate biopsies, being 79% (95% CI, 73, 85) versus 65% (95% CI, 58, 72), respectively. Estimates of PSA survival in high-risk (T2c or PSA level > 20 ng/mL or Gleason score > or = 8) and intermediate-risk patients with at least 34% positive prostate biopsies initially favored RT, but were not significantly different after 8 years. CONCLUSIONS: Intermediate-risk and low-risk patients with a low biopsy tumor volume who were treated with RP appeared to fare significantly better compared with patients who were treated using conventional-dose RT. Intermediate-risk and high-risk patients with a high biopsy tumor volume who were treated with RP or RT had long-term estimates of PSA survival that were not found to be significantly different.     

The value of digital rectal examination as a predictor of prostate cancer diagnosis among United States Veterans referred for prostate biopsy

BACKGROUND: As digital rectal examination (DRE) remains an essential part of a routine physical examination, it is important to understand its diagnostic value in different circumstances. AIM: To quantify sensitivity, specificity and predictive value of DRE as a predictor of biopsy-confirmed prostate cancer in the US Veteran population. METHODS: The study group included 628 consecutive patients who underwent transrectal biopsy for suspected prostate cancer due to abnormal digital examination of the prostate, elevated serum prostate specific antigen (PSA) or both. The DRE results reported in this study are documented during physical examinations that were performed after referral for biopsy. The relation between DRE results and positive biopsy was examined while taking into consideration demographic and clinical patient characteristics. RESULTS: Among men with normal PSA the adjusted odds ratio (OR) reflecting the association between abnormal DRE and positive prostate biopsy was 0.53 with a 95% confidence interval (CI) from 0.27 to 1.06. In the presence of a moderately elevated (4.1-10 ng/mL) PSA, the OR was 1.07 (0.72-1.60). When serum PSA exceeded 10 ng/mL, the OR was 2.15 (1.12-4.43). The positive predictive value of an abnormal DRE varied widely from as high as 81% to as low as 14% depending on the other patient characteristics. DISCUSSION: These results indicate that DRE results are most informative when evaluated in conjunction with other clinical and demographic information.     

Test sensitivity of prostate-specific antigen in the Finnish randomised prostate cancer screening trial

We estimated the sensitivity of serum prostate-specific antigen (PSA) as a screening test for prostate cancer in the Finnish randomised, population-based prostate cancer screening trial. The study population consisted of 80,458 men aged 55-67 years identified from the national population registry and randomised to the screening or control arm of the trial. The screening algorithm was based on determination of serum PSA concentration. Test sensitivity was estimated based on interval cancer incidence during the first 4 years of follow-up among screening participants with a negative screening test. Interval cancers were defined as those occurring among men with a negative screening test. Altogether, 19 interval cancers were detected among 17,897 men with serum PSA < 3 ng/ml during the first screening interval. A further 5 cases were diagnosed among 811 men with PSA 3.0-3.9 ng/ml with a benign digital rectal examination or free total PSA ratio > or = 0.16. Test sensitivity based on serum PSA of 3 ng/ml was estimated to be 0.89 (95% confidence interval 0.84-0.93) and that based on PSA of 4 ng/ml combined with an ancillary test (digital rectal examination or free total PSA ratio in the PSA range 3.0-3.9) was 0.87 (0.82-0.92). Test sensitivity achieved with serum PSA in prostate cancer screening appears excellent in the context of a population-based effectiveness trial.     

Prostate cancer-specific mortality after radical prostatectomy or external beam radiation therapy in men with 1 or more high-risk factors

BACKGROUND: Estimates of prostate cancer-specific mortality (PCSM) were determined after radical prostatectomy (RP) or radiation therapy (RT) in men with >or=1 high-risk factors. METHODS: The study cohort comprised 948 men who underwent RP (N = 660) or RT (N = 288) for localized prostate cancer between 1988 and 2004 and had at least 1 of the following high-risk factors: a prostate-specific antigen (PSA) velocity >2 ng/mL/year during the year before diagnosis, a biopsy Gleason score of >or=7, a PSA level of >or=10 ng/mL, or clinical category T2b or high disease. Grays regression was used to evaluate whether the number and type of high-risk factors were associated with time to PCSM. RESULTS: Multiple determinants of high risk were found to be significantly associated with a shorter time to PCSM after RP (P < .001) or RT (P 2 ng/mL/year was associated with an increased risk of PCSM after RP (hazards ratio [HR] of 7.3; 95% confidence interval [95% CI], 1.0-59 [P = .05]) or RT (HR of 12.1; 95% CI, 1.4-105 [P = .02]) when compared with men with any other single high-risk factor. CONCLUSIONS: Men with a PSA velocity >2 ng/mL/year had a significantly higher risk of PCSM compared with men who had any other single high-risk factor. These men should be considered for randomized trials evaluating the impact on PCSM from adding systemic agents to standards of care for men with high-risk PC.     

Prospective study of correlations between biopsy-detected high grade prostatic intraepithelial neoplasia, serum prostate specific antigen concentration, and race

BACKGROUND: High grade prostatic intraepithelial neoplasia (HGPIN), a premalignant lesion of the prostate gland, is more common in black men than in white men. The influence of HGPIN on the serum prostate specific antigen (PSA) concentration is controversial, and correlations between HGPIN and PSA in black men and white men have not been investigated. METHODS: Between January 1992 and December 1998, 411 black men and 639 white men with suspected prostate carcinoma underwent an initial benign prostate biopsy at a single medical center. The presence or absence of HGPIN in the biopsy specimens was determined by one uropathologist. RESULTS: HGPIN was identified in 8.9% of the specimens. When stratified by PSA concentration (< 4.0 ng/mL, 4.0-9.9 ng/mL, and > or = 10.0 ng/mL), HGPIN was associated with an increased PSA concentration only among men with PSA concentrations < 4.0 ng/mL (P = 0.01). The prevalence of HGPIN in the black and white patients was 13.4% and 5.9%, respectively (P < 0.0001), and was significantly greater in black men than in white men with PSA concentrations < 4.0 ng/mL (P = 0.002). Among the patients with PSA concentrations < 4.0 ng/mL, black race was an independent predictor of an increased PSA concentration when adjusted for patient age, prostate volume, and the presence or absence of HGPIN (P = 0.03). CONCLUSIONS: HGPIN is more common in black men than in white men and may produce an increase in the PSA concentration. However, racial differences in the prevalence of HGPIN may not contribute to racial differences in PSA concentrations among men with no clinical or histologic evidence of carcinoma.