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.     

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.     

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.     

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.     

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.     

Association of prostate-specific antigen promoter genotype with clinical and histopathologic features of prostate cancer

The serum test for the secreted protease prostate-specific antigen (PSA) is the most widely used screening tool for prostate cancer. The PSA gene contains multiple functional and nonfunctional single nucleotide polymorphisms (SNP) in its promoter. We showed previously that the rs925013 G/A SNP, but not the rs266882 G/A SNP, was significantly associated with serum PSA in healthy men. In this study, we evaluated the association of the PSA promoter genotype with clinical data in a cohort of 1,224 men with prostate cancer. Previous work with a subset of this cohort has shown that percent high-grade (Gleason grades 4 and 5) cancer was the strongest predictor of biochemical recurrence (PSA relapse). We found a statistically significant association (P < 0.05) of the rs925013 SNP with several clinical and histomorphologic variables. The G allele was associated with higher serum PSA at diagnosis, higher percent Gleason grade 3 cancer, and lower percent high-grade and Gleason grade 4 cancer. The rs266882 SNP was modestly associated with PSA at diagnosis in a dominant model but was not associated with cancer grade. Neither SNP was associated with biochemical recurrence. The statistically significant predictors of biochemical recurrence were tumor location in the peripheral zone [odds ratio (OR), 10.71; 95% confidence interval (95% CI), 3.15-36.49], presence of any Gleason grade 4/5 cancer (OR, 4.26; 95% CI, 1.30-14.00), presence of any intraductal cancer (OR, 1.03; 95% CI, 1.00-1.04), and serum PSA at diagnosis (OR, 2.04; 95% CI, 1.50-2.77).     

Impact of race on prostate-specific antigen outcome after radical prostatectomy for clinically localized adenocarcinoma of the prostate.

PURPOSE: To compare prostate-specific antigen (PSA) outcome after radical prostatectomy (RP) for prostate cancer in African-American and white men using previously established risk groups. PATIENTS AND METHODS: Between 1989 and 2000, 2,036 men (n = 162 African-American men, n = 1,874 white men) underwent RP for clinically localized prostate cancer. Using pretreatment PSA, Gleason score, clinical T stage, and percentage of positive biopsy specimens, patients were stratified into low- and high-risk groups. For each risk group, PSA outcome was estimated using the actuarial method of Kaplan and Meier. Comparisons of PSA outcome between African-American and white men were made using the log-rank test. RESULTS: The median age and PSA level for African-American and white men were 60 and 62 years old and 8.8 and 7.0 ng/mL, respectively. African-Americans had a statistically significant increase in PSA (P =.002), Gleason score (P =.003), clinical T stage (P =.004), and percentage of positive biopsy specimens (P =.04) at presentation. However, there was no statistical difference in the distribution of PSA, clinical T stage, or Gleason score between racial groups in the low- and high-risk groups. The 5-year estimate of PSA outcome was 87% in the low-risk group for all patients (P =.70) and 28% versus 32% in African-American and white patients in the high-risk group (P =.28), respectively. Longer follow-up is required to confirm if these results are maintained at 10 years. CONCLUSION: Even though African-American men presented at a younger age and with more advanced disease compared with white men with prostate cancer, PSA outcome after RP when controlled for known clinical predictive factors was not statistically different. This study supports earlier screening in African-American men.     

Inverse association between prostatic polyunsaturated fatty acid and risk of locally advanced prostate carcinoma

BACKGROUND: An effect of fatty acids has been implicated in men with advanced-stage prostate carcinoma and in men who have died of the disease. To evaluate the influence of fatty acids in men with prostate carcinoma at earlier stages, the authors examined the relation between prostatic concentrations of fatty acids and locally advanced prostate carcinoma in men with clinically organ-confined disease. METHODS: Fatty acids were measured by capillary gas chromatography in fresh, nonmalignant prostate tissue specimens collected during surgery from 196 men undergoing radical prostatectomy for localized prostate carcinoma. Two-sided, two-sample Student t tests compared mean concentrations in men with extraprostatic disease (pT3-4N0-1M0) with control men with organ-confined disease. Logistic regression accounted for clinical stage, prostate-specific antigen level, Gleason sum, and other factors. RESULTS: Percent total prostatic polyunsaturated fatty acid (PUFA) was found to be inversely associated with risk of locally advanced prostate carcinoma (n=52) (odds ratio [OR]=0.93, 95% confidence interval [95% CI], 0.87-0.99; P=0.035). Risk of seminal vesicle involvement accounted for this association (OR=0.86, 95% CI, 0.78-0.95; P=0.003). Percent omega-3 fatty acid (eicosapentanoic + docosahexanoic acids) and percent arachidonic acid also were found to be inversely related to the risk of seminal vesicle involvement (OR=0.52, 95% CI, 0.30-0.90; P=0.02; and OR=0.84, 95% CI,; 0.75-0.95; P=0.005, respectively). CONCLUSIONS: Prostatic PUFA levels appear to influence the risk of locally advanced prostate carcinoma in men with clinically organ-confined disease. This association may be mediated through the immune system.     

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.     

Factors affecting recurrence rates after prostatectomy or radiotherapy in localized prostate carcinoma patients with biopsy Gleason score 8 or above

BACKGROUND: To review the biochemical recurrence-free survival (bRFS) rates of treatment with either external beam radiotherapy or radical prostatectomy in patients with biopsy Gleason score 8 or above in the prostate specific antigen (PSA) era. METHODS: A total of 297 localized prostate carcinoma patients diagnosed with biopsy Gleason score 8 or above were treated between 1987 and 2000 at the Cleveland Clinic with either prostatectomy or radiotherapy (RT). All patients had pretreatment PSA (iPSA) levels. Androgen deprivation was given as part of the initial treatment in 154 patients (52%). Radical prostatectomy (RP) was the primary treatment in 115 patients (39%) and 182 patients (61%) received RT.The median radiation dose was 70.2 Gy (range, 60.0-78.0 Gy). The median follow-up time was 42 months (range, 1-153 months). RESULTS: For the 297 patients, the 5 and 8-year bRFS rates were 45% (95% confidence interval [CI] 38-52%) and 31% (95% CI 20-42%), respectively. The 5-year bRFS rates for iPSA 10 or less versus. iPSA above10 were 66% (95% CI 54-78%) versus 31% (95% CI 22-40%), respectively (P < 0.001). The 5-year bRFS rates for use of androgen deprivation versus no androgen deprivation were 62% (95% CI 52-72%) versus 35% (95% CI 27-42%), respectively (P < 0.001). The 5-year bRFS rates for RT patients versus RP patients were 47% (95% CI 38-57%) versus 42% (95% CI 31-53%), respectively (P = 0.051). For RT patients, the 5-year bRFS rates for use of androgen deprivation versus no androgen deprivation were 71% versus 29%, respectively (P < 0.001). For RP patients, the 5-year bRFS rates for use of androgen deprivation versus no androgen deprivation were 39% versus 43%, respectively (P = 0.90). Multivariate time-to-failure analysis using the proportional hazards model showed iPSA level (P < 0.001) and the use of androgen deprivation (P = 0.001) to be the only independent predictors of biochemical recurrence. Age (P = 0.44), race (P = 0.80), clinical T stage (P = 0.10), biopsy Gleason scores (P = 0.39), and treatment modality (P = 0.13) were not independent predictors of biochemical failure. A total of 104 patients had Stage T1 or T2 disease, low iPSA levels (/= 8). For all 104 patients, the 5-year bRFS rate was 64%. For 52 of the 104 patients who received 6 months of androgen deprivation or less, the 5-year bRFS rate was 78%. CONCLUSION: Patients with localized prostate carcinoma with a biopsy Gleason score 8 or less have lower recurrence rates if iPSA levels are 10 or less. Biochemical control rates were encouraging for patients with biopsy Gleason score 8 or above, clinical Stage T1-T2, and iPSA levels less than or equal to 10 ng/mL treated with adjuvant androgen deprivation given only for 6 months or less. If longer follow-up confirms these findings, these patients might not need prolonged androgen deprivation for periods exceeding 6 months following local therapy.     

Hormonal therapy or external-beam radiation with brachytherapy and the risk of death from prostate cancer in men with intermediate risk prostate cancer

Purpose

To determine whether external-beam radiotherapy (EBRT) improves disease control compared with supplemental androgen suppression therapy (AST) in men with intermediate-risk prostate cancer who are being treated with brachytherapy.

Patients and Methods

A total of 807 men with intermediate-risk prostate cancer (T2bNXM0, Gleason ≤7, prostate-specific antigen [PSA] <20 ng/mL; or cT1c-T2bNXM0, Gleason 7) were consecutively treated with either AST and brachytherapy or EBRT and brachytherapy, between 1997 and 2007, and were followed up until September 21, 2007. A Fine and Gray competing risks multivariable regression model was used to assess whether AST or radiotherapy dose escalation reduced the risk of prostate-cancer-specific mortality (PCSM) when adjusting for age, PSA, Gleason score, and tumor category.

Results

Treatment with brachytherapy and with EBRT was associated with a significant increase in the risk of PCSM compared with brachytherapy and AST (adjusted hazard ratio [HR] 4.027 [95% CI, 1.168-13.89]; P = .027) after adjusting for age and prostate cancer prognostic factors. A Gleason score of 4+3 and increasing PSA were associated with worse PCSM (adjusted HR 8.882 [95% CI, 1.095-72.04]; P = .041; and adjusted HR 8.029 [95% CI, 2.38-28.8]; P = .0014, respectively).

Conclusion

Supplemental AST use compared with EBRT is associated with a lower risk of PCSM in men with intermediate-risk PC undergoing brachytherapy. Prospective validation in a randomized controlled trial is needed.     

Influence of body mass index on prostate-specific antigen failure after androgen suppression and radiation therapy for localized prostate cancer

BACKGROUND: Increasing body mass index (BMI) is associated with shorter time to prostate-specific antigen (PSA) failure after radical prostatectomy. Whether BMI is associated with time to PSA failure was investigated in men treated with androgen suppression therapy (AST) and radiation therapy (RT) for clinically localized prostate cancer. METHODS: The observational prospective cohort study consisted of 102 men with clinically localized prostate cancer who received 70 Gy RT with 6 months of AST on a single arm of a randomized trial between December 1995 and April 2001. Height and weight data were available at baseline for 99 (97%) of the men, from which BMI was calculated. Adjusting for age (continuous) and known prognostic factors including PSA level (continuous), Gleason score, and T-category, Cox regression analyses were performed to analyze whether BMI (continuous) was associated with time to PSA failure (PSA >1.0 ng/mL and increasing >0.2 ng/mL on 2 consecutive visits). RESULTS: Median age and median BMI (interquartile range [IQR]) at baseline was 72 (69.1-74.7) years and 27.4 (24.8-30.7) kg/m,(2) respectively. In addition to an increasing PSA level (P = .006) and Gleason 8-10 cancer (P = .024), after a median follow-up (IQR) of 6.9 (5.6-8.5) years, an increasing BMI was also significantly associated with a shorter time to PSA failure (adjusted hazard ratio [HR]: 1.10; 95% confidence interval [CI]: 1.01-1.19; P = .026) after RT and AST. CONCLUSIONS: After adjusting for known prognostic factors, baseline BMI is significantly associated with time to PSA failure after RT and AST for men with clinically localized prostate cancer. Further study is warranted to assess the impact of an increasing BMI after AST administration on PSA failure, prostate cancer-specific, and all-cause mortality.     

DNA ploidy and prostate-specific antigen as prognostic factors in clinically resectable prostate cancer.

Prostate-specific antigen (PSA) and DNA ploidy as measured by flow cytometry were compared with conventional prognostic indicators in 112 patients who underwent radical prostatectomy for clinically resectable prostate cancer. The variables examined included age, race, prostatic acid phosphatase (PAP), Gleason score of the radical prostatectomy specimen, and pathologic stage. No significant relationships were found between DNA ploidy and age, mean PAP value, and absolute PAP value. Of the 112 patients, 65 (58.0%) had disease limited to the prostate (pathologic Stages A and B); 47 (42.0%) had extraprostatic disease (pathologic Stages C and D1). The stage was related to the Gleason score (P less than 0.0001) where extraprostatic disease was associated with a Gleason score of 6 to 10. Nineteen (17.0%) patients had aneuploid tumors, and 93 (83.0%) had diploid tumors. DNA ploidy significantly correlated with pathologic stage (P = 0.04); aneuploidy was identified more frequently in patients with Stages C and D1 tumors. Aneuploid tumors occurred more frequently than diploid tumors in patients with a Gleason score of 6 to 10 (P = 0.034). Mean PSA values were higher in patients with aneuploid tumors (P = 0.078), extraprostatic neoplasms (P = 0.00001), and cancers with a Gleason score of 6 to 10 (P = 0.0004). Furthermore, PSA values greater than 10.0 ng/ml were associated with extraprostatic disease and a Gleason score of 6 to 10 (P less than 0.05 and P less than 0.001, respectively). Significant racial differences were found with respect to DNA ploidy, mean DNA indices, and mean PSA values. The 18 black patients had more DNA aneuploid tumors (P = 0.043), a higher mean DNA index (P = 0.017), and a higher mean PSA value (P = 0.043) than the 94 white patients. Both PSA and DNA ploidy analysis by flow cytometry appear to be valuable indicators in the evaluation of patients with prostatic carcinoma.     

Predictors of prostate cancer-specific mortality after radical prostatectomy or radiation therapy.

PURPOSE: We evaluated predictors of prostate cancer-specific mortality (PCSM) after prostate-specific antigen (PSA) failure after radical prostatectomy (RP) or radiation therapy (RT). PATIENTS AND METHODS: A total of 1,159 men with clinically localized prostate cancer treated with RP (n = 498) or RT (n = 661) developed PSA failure, and they formed the study cohort. Competing risk regression analyses were used to evaluate whether previously identified predictors of time to metastasis, including post-treatment PSA doubling time (PSA-DT), Gleason score, and interval to PSA failure, could also predict time to PCSM after PSA failure. The cumulative incidence method was used to estimate PCSM after PSA failure. RESULTS: A post-RP PSA-DT of less than 3 months (hazard ratio [HR], 54.9; 95% CI, 16.7 to 180), a post-RT PSA-DT of less than 3 months (HR, 12.8; 95% CI, 7.0 to 23.1), and a biopsy Gleason score of 8 to 10 (HR, 6.1; 95% CI, 3.4 to 10.7) for patients treated with RT were significantly associated with PCSM. Post-RP estimated rates of PCSM 5 years after PSA failure were 31% (95% CI, 17% to 45%) v 1% (95% CI, 0% to 2%) for patients with PSA-DT of less than 3 months v > or = 3 months. Post-RT estimated rates of PCSM 5 years after PSA failure were 75% (95% CI, 59% to 92%) v 35% (95% CI, 24% to 47%) for patients with a biopsy Gleason score of > or = 8 v < or = 7, respectively, and PSA-DT of less than 3 months; these rates were 15% (95% CI, 0.8% to 28%) v 4% (95% CI, 1% to 6%), respectively, for patients with a PSA-DT > or = 3 months. CONCLUSION: Patients at high risk for PCSM after PSA failure can be identified based on post-RP PSA-DT or post-RT PSA-DT and biopsy Gleason score. These parameters may be useful in identifying patients for a randomized trial evaluating hormonal therapy with or without docetaxel.     

Agent Orange exposure, Vietnam War veterans, and the risk of prostate cancer

BACKGROUND.

It has been demonstrated that Agent Orange exposure increases the risk of developing several soft tissue malignancies. Federally funded studies, now nearly a decade old, indicated that there was only a weak association between exposure and the subsequent development of prostate cancer. Because Vietnam War veterans are now entering their 60s, the authors reexamined this association by measuring the relative risk of prostate cancer among a cohort of men who were stratified as either exposed or unexposed to Agent Orange between the years 1962 and 1971 and who were followed during the interval between 1998 and 2006.

METHODS.

All Vietnam War era veterans who receive their care in the Northern California Veteran Affairs Health System were stratified as either exposed (n = 6214) or unexposed (n = 6930) to Agent Orange. Strata‐specific incidence rates of prostate cancer (International Classification of Diseases, 9th Revision code 185.0) were calculated. Differences in patient and disease characteristics (age, race, smoking history, family history, body mass index, finasteride exposure, prebiopsy prostate‐specific antigen (PSA) level, clinical and pathologic stage, and Gleason score) were assessed with chi‐square tests, t tests, a Cox proportional hazards model, and multivariate logistic regression.

RESULTS.

Twice as many exposed men were identified with prostate cancer (239 vs 124 unexposed men, respectively; odds ratio [OR], 2.19; 95% confidence interval [95% CI], 1.75‐2.75). This increased risk also was observed in a Cox proportional hazards model from the time of exposure to diagnosis (hazards ratio [HR], 2.87; 95% CI, 2.31‐3.57). The mean time from exposure to diagnosis was 407 months. Agent Orange‐exposed men were diagnosed at a younger age (59.7 years; 95% CI, 58.9‐60.5 years) compared with unexposed men (62.2 years; 95% CI, 60.8‐63.6 years), had a 2‐fold increase in the proportion of Gleason scores 8 through 10 (21.8%; 95% CI, 16.5%‐27%) compared with unexposed men (10.5%; 95% CI, 5%‐15.9%), and were more likely to have metastatic disease at presentation than men who were not exposed (13.4%; 95% CI, 9%‐17.7%) than unexposed men (4%; 95% CI, 0.5%‐7.5%). In univariate analysis, distribution by race, smoking history, body mass index, finasteride exposure, clinical stage, and mean prebiopsy PSA were not statistically different. In a multivariate logistic regression model, Agent Orange was the most important predictor not only of developing prostate cancer but also of high‐grade and metastatic disease on presentation.

CONCLUSIONS.

Individuals who were exposed to Agent Orange had an increased incidence of prostate cancer; developed the disease at a younger age, and had a more aggressive variant than their unexposed counterparts. Consideration should be made to classify this group of individuals as ‘high risk,’ just like men of African‐American heritage and men with a family history of prostate cancer. Cancer 2008. © 2008 American Cancer Society.     

Time to an undetectable prostate-specific antigen (PSA) after androgen suppression therapy for postoperative or postradiation PSA recurrence and prostate cancer-specific mortality

BACKGROUND: For men receiving androgen-suppression therapy (AST) for a rising postoperative or postradiation prostate-specific antigen (PSA) recurrence, whether the time to an undetectable (u) PSA was significantly associated with prostate cancer-specific mortality (PCSM) was evaluated. METHODS: The study cohort comprised 585 men with a rising PSA and negative bone scan after surgery (n = 415) or radiation therapy (n = 170) that were treated with AST and achieved a uPSA. Gray's regression was used to evaluate whether the time to a uPSA after AST was significantly associated with the time to PCSM after the uPSA adjusting for known prognostic factors. RESULTS: The median time (interquartile range) to achieve a uPSA was 4.6 (range, 2.8-7.8) months. There were 23 deaths, 4 of which were from prostate cancer. An increasing time to a uPSA (adjusted hazard ratio [HR]: 9.2, 95% confidence interval [CI]: 3.8, 22.1; P < .0001), a decreasing PSA doubling time (DT) (HR: 0.58, 95% CI: 0.43, 0.80; P = .0007), and Gleason score 8 to 10 cancers (HR: 8.6, 95% CI: 1.04, 77; P = .05) were significantly associated with a shorter time to PCSM. CONCLUSIONS: Despite achieving a uPSA after AST, the risk of PCSM increased significantly as the time to the uPSA lengthens, especially in men with a short pre-AST PSA DT and high-grade prostate cancer. These men should be considered for randomized studies evaluating immediate vs delayed chemotherapy after the achievement of the uPSA.     

Serum insulin level,disease stage,prostate specific antigen (PSA) and Gleason score in prostate cancer

In the present study, we assessed the relationship of serum insulin levels and three surrogate markers of recurrence, T stage, PSA, and Gleason score, in men with localized prostate cancer. Participants in our study were found through urology and radiation oncology clinics, and all eligible patients were asked to take part. All patients were asymptomatic and had been initially diagnosed on the basis of rising PSA or abnormal physical examination. Histological confirmation of diagnosis was obtained for all subjects. Serum insulin levels were determined by chemoluminescent assay with a standard, commercially available instrument. Patients were divided into three previously defined risk groups: Low risk: PSA < or =10, stage < or =T2a, or Gleason grade < or =6. Medium risk: 10 7, tumour in seminal vesicle biopsy, PSA >15 or stage T2c or T3. One hundred and sixty-three men with prostate cancer were studied. There was a significant increase in serum insulin with risk group (P=0.003, one way anova). Tukey's multiple range test showed that the insulin levels of high risk patients were significantly higher than the insulin levels of medium and low risk patients (P=0.05) but the insulin levels of medium and low risk patients were not significantly different from one another. Multivariate linear regression, with insulin as the dependent variable, Gleason score, PSA, and T stage (T1, T2, T3) as the independent variables, was significant overall (P<0.001, r(2)=0.120). Increased T stage was independently correlated with increased serum insulin levels (P<0.001). Gleason score was negatively, insignificantly correlated with serum insulin level (P=0.059). The positive correlation of PSA and insulin level was not significant (P=0.097). To assure normal distribution of insulin and PSA values, the regression was repeated with log (insulin) as the dependent variable, log (PSA), T stage (T1, T2, T3), and Gleason score as independent variables. The regression was significant overall (P=0.002, r(2) =0.095). Increased T stage was independently correlated with increased log (insulin level) (P=0.026). Gleason score was negatively, insignificantly correlated with log (insulin) level (P=0.728). The positive correlation of log (PSA) and log (insulin) levels was significant (P=0.010). The relationship between increased insulin level and advanced tumour stage in prostate cancer we describe here is biologically quite plausible, since insulin is a growth factor. Further studies may document whether serum insulin levels might be a useful biomarker of prostate cancer stage.     

Sex steroid hormones and the androgen receptor gene CAG repeat and subsequent risk of prostate cancer in the prostate-specific antigen era.

OBJECTIVE: Sex steroid hormones are thought to contribute to the growth, differentiation, and progression of prostate cancer. We investigated plasma levels of sex steroid hormones and length of the androgen receptor gene CAG repeat in relation to incident prostate cancer diagnosed in the prostate-specific antigen (PSA) era.METHODS: Using a nested case-control design, we included 460 prostate cancer cases diagnosed after providing a blood specimen in 1993 but before February 1998 among men in the Health Professionals Follow-up Study. Controls were 460 age-matched men without prostate cancer who had a screening PSA test after the date of providing a blood specimen. We measured plasma concentrations of total testosterone, free testosterone, dihydrotestosterone, androstanediol glucuronide, estradiol, and sex hormone binding globulin (SHBG) and determined the length of the androgen receptor gene CAG repeat. Conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) of prostate cancer.RESULTS: Mean concentrations of the sex steroids adjusted for SHBG, and mean CAG repeat length did not differ significantly between the prostate cancer cases and controls. No significant associations with total prostate cancer were detected for plasma total testosterone concentration (comparing highest versus lowest quartiles: OR, 0.78; 95% CI, 0.48-1.28; P(trend) = 0.73) or the other sex hormones after adjusting for SHBG. However, plasma total testosterone concentration was positively associated with low-grade disease (Gleason sum < 7: OR, 1.91; 95% CI, 0.89-4.07; P(trend) = 0.02) and inversely associated with high-grade disease (Gleason sum > or = 7: OR, 0.26; 95% CI, 0.10-0.66; P(trend) = 0.01). Similar patterns for grade were observed for free testosterone. Short CAG repeat length was not associated with total prostate cancer (< or = 19 versus > or = 24: OR, 0.84; 95% CI, 0.57-1.23; P(trend) = 0.22) or grade of disease. No clear associations with regionally invasive or metastatic (> or = T3b, N1, or M1) were found for any of the hormones or the CAG repeat, although the number of these cases was small.CONCLUSIONS: The overall lack of association of prostate cancer diagnosed in the PSA era with sex steroid hormones and the androgen receptor gene CAG repeat length is consistent with the hypothesis that these factors do not substantially contribute to the development of early prostate cancer in the PSA era. The influence of plasma total and free testosterone concentrations on prostate cancer grade merits further evaluation.     

血清缓激肽与前列腺癌的相关性研究

目的 探讨血清缓激肽在前列腺癌的诊断及鉴别诊断中的临床应用价值.方法 收集68例前列腺癌患者和32例前列腺增生患者,以同期体检的健康男性32例为对照组,收集其血清,酶联免疫吸附试验(enzymelinked immuno sorbent assay,ELISA)法检测血清中的缓激肽水平,比较各组血清缓激肽水平的差异以及前列腺癌患者在不同年龄、临床分期、病理分期(Gleason评分)、前列腺特异抗原(prostate specific antigen,PSA)水平、肿瘤体积以及骨转移、淋巴结转移、局部侵犯与否状态下血清缓激肽水平的差异.比较血清缓激肽与PSA联合诊断前列腺癌和PSA独立诊断前列腺癌的敏感度差异.结果 前列腺癌组血清缓激肽水平[(16.44 ±0.91) μg/L]低于对照组[(19.72±1.10) μg/L]和前列腺增生组[(20.93±1.80) μg/L],差异均具有统计学意义(均P＜0.05).在肿瘤体积较大的前列腺癌患者血清缓激肽水平较低(P＜0.05),而血清缓激肽水平在年龄、肿瘤临床分期、病理分期(Gleason评分)、PSA水平及骨转移、淋巴结转移、局部侵犯与否方面比较差异均无统计学意义(均P＞0.05).血清缓激肽与PSA联合诊断前列腺癌较单独诊断敏感度提高(P＜0.05).结论 前列腺癌患者血清缓激肽表达水平较低,且与肿瘤体积相关.血清缓激肽与PSA联合诊断前列腺癌敏感度较单独诊断高.