Serum keratinocyte growth factor measurement in patients with prostate cancer

PURPOSE: Keratinocyte growth factor (KGF) is a stromally derived growth factor important in mediating androgen induced activities in benign prostatic hyperplasia (BPH) and prostate cancer. We assessed whether serum KGF could be used as a molecular marker in patients with prostate cancer. MATERIALS AND METHODS: Using a modified double sandwich enzyme-linked immunosorbent assay, we measured serum KGF in 56 men with prostate cancer and 81 men with BPH. Comparative analyses were made with total serum prostate specific antigen (PSA), disease stage and clinical grade. RESULTS: Following optimization, a sensitive and reproducible assay for serum KGF measurement was developed. Serum KGF levels tend to be higher in men with BPH compared to those with prostate cancer (1,242 and 828 pg./ml., respectively). A weak but significant linear relationship between PSA and KGF (p = 0.034) was found in patients with BPH. There was no association between KGF and tumor grade or stage but there was a strong positive linear relationship between PSA and KGF (p = 0.006, R(2) = 68.3%) in low grade tumors. In those men with serum PSA less than 10 ng./ml. KGF levels were significantly higher in BPH compared to prostate cancer cases (965 +/- 245 and 133 +/- 61.3 pg./ml., respectively, p = 0.0058). Using a KGF threshold range of 500 to 900 pg./ml., specificity for detecting BPH was 88% to 100% and the positive predictive value was 92% to 100%. CONCLUSIONS: We have optimized a reproducible and sensitive enzyme-linked immunosorbent assay system for the measurement of serum KGF. Overall KGF levels tend to be lower in patients with prostate cancer than with BPH. In patients with serum PSA less than 10 ng./ml. serum KGF levels were significantly higher in the BPH compared to the prostate cancer group. A large prospective study is indicated to assess the role of serum KGF measurement in patients with prostate cancer.     

Relationship between lower urinary tract symptoms and serum levels of sex hormones in men with symptomatic benign prostatic hyperplasia

Study Type – Aetiology (case series)
Level of Evidence 4

OBJECTIVES

To investigate a possible association between the severity of lower urinary tract symptoms (LUTS) and the serum levels of sex hormones in men with symptomatic benign prostatic hyperplasia (BPH) that underwent surgery for severe benign prostatic obstruction.

PATIENTS AND METHODS

In all, 127 selected men with symptomatic BPH attending our urology clinic were recruited. The clinical conditions of BPH were assessed by digital rectal examination, serum prostate‐specific antigen (PSA) determination, International Prostate Symptom Score (IPSS), transrectal ultrasonography and maximum urinary flow rate (Q_max) value at uroflussimetry. Before surgery, we measured the serum concentrations of total testosterone (TT) and free testosterone (FT), oestradiol, prolactin, luteinizing hormone and follicle‐stimulating hormone. We excluded men with endocrine diseases, those with prostate disease who were receiving antiandrogen therapy and those with psychological diseases. The relationships between the IPSS score and serum sex hormone levels were determined.

RESULTS

The final study population consisted of 122 men (mean age of 70.66 years), as five were excluded (three due to incomplete evaluation and two who were diagnosed with prostate cancer). On statistical analysis, the total IPSS was significantly associated with age (r= 0.405, P < 0.001) and TT (r= 0.298, P= 0.020) but not with FT or the serum levels of the other sex hormones. The serum levels of testosterone and IPSS did not correlate with prostate volume and Q_max. PSA level and age correlated with prostate volume (r= 0.394, P < 0.001; r = 0.374, P < 0.001, respectively). We distinguished two subgroups of patients: the first group of 40 men with an IPSS of <19 and the second group of 82 with an IPSS of >19, and we evaluated the median levels of TT in each group. There was an increased risk of LUTS in men with a greater serum concentration of TT (P= 0.042), although the mean TT level was in the normal range.

CONCLUSIONS

In the present study, the severity of LUTS was associated with age and serum levels of TT but only age correlated with the measures of BPH, especially prostate volume. The potential effects of testosterone on LUTS may well be indirect. Additional large studies are needed to confirm these preliminary results.     

Putative protein markers in the sera of men with prostatic neoplasms

OBJECTIVE: To describe the preliminary identification of serum proteins that may be diagnostic markers in prostate cancer. PATIENTS AND METHODS: The study included 11 men referred for treatment of localized prostate cancer, 12 with benign prostatic hyperplasia (BPH) and 12 disease-free controls. For serum protein analysis, the protein-chip array surface-enhanced laser desorption/ionization (SELDI) technique was used (Ciphergen Biosystems, Fremont, CA). SELDI combines protein-chip technology with time-of-flight mass spectrometry, and offers the advantages of speed, simplicity and sensitivity. RESULTS: Three protein peaks were identified in the serum of men with prostate cancer and BPH, but not in controls, with relative molecular masses of 15.2, 15.9 and 17.5 kDa. These three proteins were significantly associated with BPH and prostate cancer when compared with controls (P = 0.001, 0.004, and 0.011, respectively, Kruskal-Wallis test). Interestingly, the 17.5 kDa protein was more abundant in five men with stage T1 prostate cancer than in eight with stage T2 (P = 0.016, two tailed Mann-Whitney U-test corrected for ties). CONCLUSIONS: These proteins, particularly the 15.9 kDa one, may be used for the diagnosis or monitoring of prostate cancer and differentiation from BPH, and have the potential for antibody-based chip SELDI-TOF technology. Identified proteins may be targets for immunotherapy.     

Obesity in relation to prostate cancer risk: comparison with a population having benign prostatic hyperplasia

OBJECTIVE: To analyse the relationship between obesity and prostate cancer, when compared with men with benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: The records were reviewed of consecutive patients with histologically confirmed prostate cancer admitted for prostate surgery between January 1993 and February 1999. Controls were selected from patients who were hospitalized at the same time for the surgical treatment of BPH. One control was matched to each case by age. Obesity was defined as a body mass index (BMI) of> 29 kg/m2. RESULTS: The study included 194 cases and 194 controls; their median (range) age at operation was 69.5 (50-88) years in both groups, and the BMI 26.1 (16.6-38.1) kg/m2 in the cancer and 25.7 (15.1-36.8) kg/m2 in the BPH group. The difference between the groups was not significant (P = 0.06). Obesity was significantly associated with prostate cancer, with an odds ratio (95% confidence interval) of 2.47 (1.41-4.34). Cases with advanced disease had a higher BMI than those with localized disease, but when age was considered the difference was not significant. CONCLUSION: In general the BMI was not significantly associated with prostate cancer when compared with men having BPH. However, obese men had 2.5 times the risk of having prostate cancer.     

Significance of vitamin D receptor gene polymorphism for risk and disease severity of prostate cancer and benign prostatic hyperplasia in Japanese

OBJECTIVE: Recent studies have demonstrated an association between vitamin D receptor (VDR) genotype and prostate cancer. Currently, there is a scarcity of data regarding the association of VDR genotype with benign prostatic hyperplasia (BPH). The purpose of this study was to investigate the TaqI VDR polymorphism in Japanese prostate cancer patients, Japanese BPH patients and Japanese controls in order to determine if an association exists between VDR genotype and the risk of developing prostate cancer and BPH as well as disease severity. METHODS: 110 prostate cancer patients, 83 BPH patients and 90 male age-matched controls were genotyped for a previously described TaqI restriction fragment length polymorphism at codon 352 in exon 9 of the VDR gene. Products were digested into T allele or t allele according to the absence or presence of a TaqI restriction site with individuals being classified as TT, Tt or tt. RESULTS: The frequency of the genotype tt was higher in the control group (6.7%) compared to patients with prostate cancer (1.8%) and BPH (3.6%) but this was not statistically significant. However, the frequency of the genotype TT was significantly higher among prostate cancer patients with locally advanced or metastatic disease (T3/ T4/N1/M1) compared to controls (p = 0.001). In addition, the genotype TT was significantly higher among prostate cancer patients with a high Gleason grade of tumor (grade 5) compared to controls (p = 0.0001). In addition, the genotype TT was statistically higher in BPH patients with high prostate volume (volume >50 cm(3)) compared to controls (p = 0.001). CONCLUSION: These data demonstrate that VDR genotype plays an important role in determining the risk of more advanced and aggressive prostate cancer as well as prostatic enlargement in Japanese men.     

MOLECULAR GENETIC PROFILING OF GLEASON GRADE 4/5 PROSTATE CANCERS COMPARED TO BENIGN PROSTATIC HYPERPLASIA

PURPOSE: Because Gleason grade 4/5 cancer is the primary cause of failure to cure prostate cancer, we examined the molecular profiles of this high grade cancer in search of potentially new therapeutic interventions as well as better serum markers than prostate specific antigen. MATERIALS AND METHODS: We compared the gene expressions in fresh frozen tissues from 9 men with Gleason grade 4/5 cancer to 8 men with benign prostatic hyperplasia (BPH) treated with radical retropubic prostatectomy. Labeled complementary RNA from each of the 17 tissues was applied to HuGeneFL probe arrays representing approximately 6,800 genes (Affymetrix, Inc., Santa Clara, California). After removing all genes undetectable in BPH and grade 4/5 cancers, and transforming the data into a parametric distribution, we chose only those up and down-regulated genes with a p difference in fluorescence between grade 4/5 cancer and BPH of p <0.0005. This value reduced the data set to 40 up-regulated and 111 down-regulated genes. We then eliminated all genes that were not expressed in all 8 BPH and 9 grade 4/5 tissues, which produced a final set of 86 genes, of which 22 were up-regulated and 64 were down-regulated. RESULTS: Cluster analysis cleanly separated men with grade 4/5 cancers from those with BPH. Only 17 of the 86 candidate genes (20%) were known to be prostate cancer related and 42 (49%) were related to other cancers. The most up-regulated gene is Hepsin, a trypsin-like serine protease with its enzyme catalytic domain oriented extracellularly. Prostate specific membrane antigen is the second most up-regulated gene (all other reports on prostate specific membrane antigen have been at the protein level). The genes for prostate specific antigen (hK3) and human glandular kallikrein2 (hK2) showed equivalent expression levels 10 times the average of other genes. Complete lists of all 22 up-regulated genes and 64 down-regulated genes, together with their locus on the chromosome, are presented in rank order. CONCLUSIONS: We characterize for the first time 64 down-regulated and 22 up-regulated genes in Gleason grade 4/5 cancer, using the gene profile from BPH as control tissue. A number of interesting new genes, previously undescribed in prostate cancer, are presented as possibilities for further study.     

Calculated fast-growing benign prostatic hyperplasia--a risk factor for developing clinical prostate cancer

OBJECTIVE: Whether there is an association between the development of benign prostatic hyperplasia (BPH) and clinical prostate cancer is controversial. The present report tests the hypothesis of an association between BPH growth and the development of clinical prostate cancer by examining stage, grade and PSA-level in men with recently discovered clinical prostate cancer with slow or fast-growing BPH. If the hypothesis is true, men with fast-growing BPH would have a more advanced clinical prostate cancer. MATERIAL AND METHODS: Two hundred and twenty patients in whom a clinical prostate cancer was diagnosed were consecutively included. The prevalence of atherosclerotic disease, non-insulin-dependent diabetes mellitus (NIDDM) or treated hypertension was provided by the respective patient's medical history. Tallness, body weight, waist measurement, hip measurement and blood pressure were determined. The body mass index (BMI) and waist/hip ratio (WHR) were calculated. Blood samples were drawn to determine triglycerides, total cholesterol, HDL-cholesterol, LDL-cholesterol, uric acid, ALAT and the fasting plasma insulin level. The prostate gland volume was measured using transrectal ultrasound. The annual BPH growth rate was calculated, assuming that the total prostate gland volume was 20 mL at the patient age of forty. The prostate cancer diagnosis was established using the technique of transrectal ultrasound-guided automatic needle biopsy of the prostate. RESULTS: Men with clinical prostate cancer, PSA <50 ng/mL, and with fast-growing BPH had a higher systolic (p = 0.009) and diastolic (p = 0.020) blood pressure, were taller (p < 0.001) and more obese, as determined by body weight (p < 0.001), BMI (p = 0.005), waist measurement (p < 0.001) and hip measurement (p = 0.003). They also had a higher fasting plasma insulin level (p = 0.014) and a lower HDL-cholesterol level (p = 0.067) than men with slow-growing BPH. Moreover, men with clinical prostate cancer, PSA <50 ng/mL, and fast-growing BPH had more pronounced clinical prostate cancer, as measured by grade (p = 0.029) and PSA-level (p = 0.016), than men with slow-growing BPH. In the total material, including men with clinical prostate cancer, PSA >/=50 ng/mL, men with fast-growing BPH also had a higher prevalence of NIDDM (p = 0.039) and a borderline statistical significance for higher stage (p = 0.09) than men with slow-growing BPH. The BPH growth rate was significantly associated with the clinical prostate cancer grade (p = 0.018) and PSA-level (p = 0.002) but not with the clinical cancer stage in a multivariate statistical analysis. CONCLUSIONS: This report confirms findings in previous studies that fast-growing BPH is a risk factor for NIDDM, hypertension, tallness, obesity, dyslipidaemia and hyperinsulinaemia. The present report extends this list of risk factors to include atherosclerotic disease manifestations, hyperuricaemia and higher ALAT levels. The study suggests that fast-growing BPH is a risk factor for developing clinical prostate cancer and, thus, supports the hypothesis of an association between the development of BPH and clinical prostate cancer. The study generates the hypothesis that clinical prostate cancer is a component of the metabolic syndrome and that insulin is a promoter of clinical prostate cancer.     

Influence of prostate volume and percent free prostate specific antigen on prostate cancer detection in men with a total prostate specific antigen of 2.6 to 10.0 ng/ml

PURPOSE: Percent free prostate specific antigen and prostate specific antigen density have been independently shown to increase the specificity of prostate cancer screening in men with prostate specific antigen levels between 4.1 and 10.0 ng/ml. Recent data suggest the total prostate specific antigen cutoff for performing a biopsy should be 2.6 ng/ml. We assessed the influence of percent free prostate specific antigen and prostate volume on cancer detection in men with a prostate specific antigen between 2.6 and 10.0 ng/ml. MATERIALS AND METHODS: From 1991 to 2005 all transrectal ultrasound guided prostate biopsies (5,587) for abnormal digital rectal examination and/or increased age specific prostate specific antigen were evaluated. A total of 1,072 patients with a prostate specific antigen between 2.6 and 10.0 ng/ml and any percent free prostate specific antigen were included in study. The cancer detection rate was calculated for each percent free prostate specific antigen/volume stratum. RESULTS: Prostate cancer was detected in 296 patients (27.6%). The mean age and prostate specific antigen of the patients with benign pathology and prostate cancer were similar. Mean percent free prostate specific antigen was 17.5% and 14.1% (p>0.05), and the mean volume was 62.0 and 46.0 cc (p=0.001), respectively. The strongest risk factors for a positive biopsy were percent free prostate specific antigen (odds ratio 0.004, p<0.001), volume (OR 0.977, p<0.001) and digital rectal examination (OR 1.765, p=0.007), but not total prostate specific antigen (p=0.303). When stratified by volume and percent free prostate specific antigen, distinct risk groups were identified. The probability of detecting cancer inversely correlated with prostate volume and percent free prostate specific antigen. CONCLUSIONS: In men with prostate specific antigen levels between 2.6 and 10.0 ng/ml, the probability of detecting cancer was inversely proportional to prostate volume and percent free prostate specific antigen. This table may assist in predicting patient risk for harboring prostate cancer.     

A population based study of incidence and treatment of benign prostatic hyperplasia among residents of Olmsted County, Minnesota: 1987 to 1997

PURPOSE: The treatment of benign prostatic hyperplasia (BPH), a common problem faced by aging men, has changed dramatically during the last decade. While BPH has long been considered a surgical condition, the advent of less invasive therapies makes the evaluation of the use of these various treatments important. Thus, this population based study was undertaken to describe the incidence and treatment for BPH from 1987 to 1997 among residents of Olmsted County, Minnesota. MATERIALS AND METHODS: We identified all Olmsted County men with a new diagnosis of BPH from 1987 to 1997 through the Medical and Surgical Indices made available through the Rochester Epidemiology Project. Overall year and age specific incidence rates were calculated for diagnosed BPH and by treatment type (surgical, minimally invasive, pharmacological, watchful waiting) assuming all men of the Olmsted County population to be at risk. Temporal changes in incidence were analyzed by Poisson regression. RESULTS: From 1987 to 1997, 2,330 cases of BPH were identified representing an age adjusted, corrected incidence for BPH among male residents of Olmsted County of 854.7 per 100,000 men. While the incidence of BPH increased from 1987 to 1992, coinciding with the introduction of serum prostate specific antigen testing, and subsequently decreased through 1997, the overall incidence of BPH decreased during the 10-year period for the entire cohort (p =0.002). Although the incidence of watchful waiting appeared to increase in the mid 1990s, significant decreases in age adjusted incidence were observed for the period overall (p <0.001). Significant decreases in surgical treatments were observed (p <0.0001). In contrast, there were significant increases in the age adjusted rates of pharmacological treatments during the 10 years (p <0.0001). No significant differences in incidence patterns of treatment type over time were observed by age group. CONCLUSIONS: The introduction of serum prostate specific antigen testing as a screening tool for prostate cancer along with the advent of less invasive alternatives, including pharmacological therapy, have had a significant impact on the incidence of diagnosed BPH in the last decade.     

THE EFFECT OF HIGH GRADE PROSTATIC INTRAEPITHELIAL NEOPLASIA ON SERUM TOTAL AND PERCENTAGE OF FREE PROSTATE SPECIFIC ANTIGEN LEVELS

PURPOSE: It is established that the percentage of free prostate specific antigen (PSA) in serum is low in patients with prostate cancer. An unanswered question is whether a low percentage of free PSA can be explained by high grade prostatic intraepithelial neoplasia alone. We compared the percentage of free PSA in men with high grade prostatic intraepithelial neoplasia alone, prostate cancer, benign prostatic hyperplasia (BPH) and a normal prostate (that is normal digital rectal examination and PSA less than or equal to 2.5 ng./ml.). MATERIALS AND METHODS: From October 1994 through December 1997, 48 men were diagnosed with high grade prostatic intraepithelial neoplasia without concomitant prostate cancer. Of these men 43 with a mean age plus or minus standard deviation of 67.4 +/- 7.8 years comprised our study group. To date none has been diagnosed with cancer during followup. Serum free and total PSA levels were measured, and the percentage of free PSA was calculated. The percentage of free PSA in the 43 men was compared to that in 50 with prostate cancer (mean age 65.4 +/- 7.8 years), 50 with biopsy proved BPH (67 +/- 7) and 43 with a normal prostate (61 +/- 8). RESULTS: There was no significant difference in mean total serum PSA in patients with high grade prostatic intraepithelial neoplasia, prostate cancer or BPH. The percentage of free PSA was significantly lower in patients with prostate cancer (14.9 +/- 6.5%) than those with high grade prostatic intraepithelial neoplasia (20.8 +/- 7.1%), BPH (20.1 +/- 7.3%) or a normal prostate (27.7 +/- 12.2%). There was also no significant difference in the percentage of free PSA between men with high grade prostatic intraepithelial neoplasia (20.8 +/- 7.1%) and those with BPH (20.1 +/- 7.3%). Additionally, men with a normal prostate had a higher percentage of free PSA (27.7%) than those with BPH (20.1%), high grade prostatic intraepithelial neoplasia (20.8%) or prostate cancer (14.9%). CONCLUSIONS: The percentages of free PSA in men with high grade prostatic intraepithelial neoplasia and BPH are similar, and significantly higher than those found in men with prostate cancer.     

Chronic kidney disease among men with lower urinary tract symptoms due to benign prostatic hyperplasia

Study Type – Diagnosis (case series)
Level of Evidence 4

OBJECTIVE

To analyse potential association of various clinical characteristics of benign prostatic hyperplasia (BPH) with chronic kidney disease (CKD) among men presenting with lower urinary tract symptoms (LUTS) secondary to BPH of varying severity.

PATIENTS AND METHODS

We reviewed the data of 2741 consecutive patients who presented to our clinic with LUTS secondary to BPH. For our analysis, CKD was defined by an elevated serum creatinine level or decreased estimated glomerular filtration rate (eGFR). Univariate and multivariate logistic regression analyses were used to address associations of CKD with various clinical characteristics.

RESULTS

Of the 2741 patients, 161 (5.9%) were initially classified as having CKD (serum creatinine ≥133 µmol/L). In multivariate analysis, peak flow rate (P = 0.001) and a history of hypertension and/or diabetes (both P < 0.001) were significantly associated with CKD, whereas age, body mass index, prostate‐specific antigen level, prostate volume, postvoid residual, or International Prostate Symptom Score (IPSS) were not. When individual symptoms from the IPSS were analysed, only weak stream (P = 0.041) and hesitancy (P = 0.048), both obstruction‐related, were significantly associated with CKD status in age and comorbidity‐adjusted analyses. The results of secondary analysis with CKD defined as an eGFR of <60 mL/min/1.73 m² were similar.

CONCLUSION

Our results show that decreased peak flow rate and a history of hypertension and/or diabetes are significantly associated with CKD in men seeking management for LUTS from BPH of varying severity.     

Benign prostatic hyperplasia: racial differences in treatment patterns and prostate cancer prevalence

Study Type – Prevalence (prospective cohort with good follow‐up) Level of Evidence 1b What’s known on the subject? and What does the study add? Previous studies evaluating racial differences in BPH treatment and outcomes have concluded that more attention in the management of lower urinary tract symptoms should be directed at African Americans. Although the relationship between BPH and the development of prostate cancer is inconclusive, longitudinal studies have indicated racial disparities in the incidence of prostate cancer. This is the first long‐term follow‐up study in a BPH population to assess the incidence of prostate cancer among African American and Caucasian men under “real‐world” clinical practice circumstances. This study suggests that African Americans with BPH have a much greater risk of developing prostate cancer than similar Caucasian men, highlighting the need for education, prevention and early detection.

OBJECTIVE

? To compare prostate cancer, prostate‐related surgery and acute urinary retention rates, as well as associated healthcare resource use over 11 years in African American and Caucasian men with benign prostatic hyperplasia (BPH).

PATIENTS AND METHODS

? The BPH‐related medical and surgical charges and events were determined for 398 African American men and 1656 Caucasian men followed for a mean of 10.2 years within a health maintenance organization. ? Racial differences in clinical outcomes were evaluated using time‐to‐event analysis, stratifying results by baseline prostate‐specific antigen (PSA) values.

RESULTS

? Risk of a prostate cancer diagnosis was 2.2 times greater in African American than Caucasian men (95% CI 1.48–3.35, P < 0.001) in analyses adjusting for serum PSA level. ? Although African Americans were more likely to receive medical therapy for symptoms of BPH than Caucasians (43.5% vs 37.2%, respectively; P= 0.029), there were no clinically meaningful differences with respect to subsequent acute urinary retention or BPH‐related surgery between them, or BPH‐related medical charges (US $407 vs US $405 per month).

CONCLUSION

? As evidenced by this analysis of ‘real‐world’ clinical practice, African Americans with BPH have a much greater risk of developing prostate cancer than similar Caucasian men highlighting the need for education and early detection in this population.     

Urinary PSA: a potential useful marker when serum PSA is between 2.5 ng/mL and 10 ng/mL

Introduction

Our objective was to evaluate the usefulness of urinary prostate specific antigen (PSA) in the differential diagnosis of benign prostatic hyperplasia (BPH) and prostate cancer.

Methods

We undertook a prospective study and obtained informed consent from 170 men. They provided blood samples to measure serum PSA and 50 mL of first-voided urine to measure urinary PSA. Seventy-seven men were diagnosed with BPH; 42 patients had newly diagnosed prostate cancer; and 51 were selected as age-matched control subjects. Data were analyzed using Wilcoxon signed rank tests, receiver operating characteristic (ROC) curves and logistic regression.

Results

Prostate volume was 35 cm³ and 45 cm³ (p < 0.05), serum PSA was 9.7 ng/mL and 4.5 ng/mL (p < 0.001) and PSA density was 0.28 and 0.11 (p < 0.01) for prostate cancer and BPH patients, respectively. Overall, urinary PSA was not significantly different, but PSA ratio (urinary:serum) was significantly different at 6.7 and 30.6 (p < 0.001) for prostate cancer and BPH patients, respectively. A subgroup with serum PSA between 2.5 ng/mL and 10.0 ng/mL was selected and urinary PSA was significant: 52.6 ng/mL (n = 29) and 123.2 ng/mL (n = 35) (p < 0.05) for prostate cancer and BPH patients, respectively. PSA ratios were also significant (p = 0.007). ROC curves identified a cutoff for urinary PSA at > 150 ng/mL, with a sensitivity of 92.5%. When comparing prostate cancer patients with age-matched control subjects, serum PSA, urinary PSA and PSA ratio were different (p = 0.004).

Conclusion

Our study supports urinary PSA as a useful marker in the differential diagnosis of prostate cancer and BPH, especially when serum PSA is between 2.5 ng/mL and 10 ng/mL. Low urinary PSA and PSA ratios point toward prostate cancer. A urinary PSA threshold of > 150 ng/mL may be used to decrease the number of prostatic biopsies.     

上海市BPH人群中PSA的年龄特异性分布

目的：建立上海市BPH人群的血清总前列腺特异抗原（T-PSA）的各年龄段特异性的参考值范围。方法：收集2006年12月-2008年4月上海交通大学附属第一人民医院BPH及可疑前列腺癌的4185例上海患者的血清T—PSA值及游离PSA（F—PSA）值。所有患者均有国际前列腺症状评分（I-PSS）、B超检查及直肠指诊。采用单因素直线回归分析方法分析患者T—PSA、F-PSA及F／T比值与年龄的关系。结果：4110例BPH患者血清T—PSA及F-PSA与年龄呈正相关（r=0．28,P〈0．0001及r=0．28,Pd0．0001）,F／T比值与年龄呈负相关（r=-0．05,P=0．0005）;上海市人群T—PSA值的年龄特异性分布大致为：40～49岁者为0～2．2ng／ml,50～59岁者为O～3．4ng／ml,60～69岁者为0～5．5ng／ml,70～79岁者为O～6．7ng／ml,80～89岁者为O～8．4ng／ml,90～99岁者为0～9．4ng／ml。上海市BPH人群较北京市BPH人群各年龄段特异性T-PSA值高,差异有显著统计学意义（t=4．63,P=0．01）;较西安市健康人群高,差异有显著统计学意义（t=3．42,P=0．04）;较黑人社区人群低,差异有显著统计学意义（t=-0．62,P=0．0085）。结论：上海市BPH患者血清T—PSA和F-PSA水平与年龄呈正相关,而F／T比值与年龄呈负相关。血清T—PSA的年龄特异性分布有地区及种族差异。     

Percent Gleason grade 4/5 as prognostic factor in prostate cancer diagnosed at transurethral resection

PURPOSE: We investigated the value of percent Gleason grade 4/5 as a predictor of long-term outcome in men with prostate cancer diagnosed at transurethral resection who received deferred treatment. MATERIALS AND METHODS: A series of 305 men with prostate cancer diagnosed at transurethral resection from 1975 to 1990 who had subsequent expectancy was analyzed. Mean patient age at diagnosis was 74 years (range 52 to 95). Slides were reviewed, and the Gleason score, percent Gleason grade 4/5 and modified Gleason score (the sum of the dominant and worst grades) were assessed. RESULTS: At followup 271 men (89%) had died, including 110 (36%) of prostate cancer. Gleason score, percent Gleason grade 4/5 and modified Gleason score were significant predictors of disease specific survival (p <0.001). Of all men 34% had tumors without any grade 4/5 pattern, of whom only 8% died of prostate cancer compared with 52% with any grade 4/5 pattern (p <0.001). Gleason score 6 tumors with focal grade 4 (less than 5%) had a worse prognosis than pure Gleason score 3 + 3 = 6 tumors (p = 0.008). There was nonsignificantly shorter survival for Gleason score 4 + 3 = 7 than for Gleason score 3 + 4 = 7 disease (p = 0.19). In Cox models including all possible pairs of Gleason score, percent Gleason grade 4/5 and modified Gleason score the percent Gleason grade 4/5 and modified Gleason score were stronger than Gleason score, although all 3 were independently significant prognosticators. CONCLUSIONS: Percent Gleason grade 4/5, modified Gleason score and Gleason score are predictors of disease specific survival in patients with prostate cancer on deferred treatment. Our study indicates that any grade 4/5 pattern impairs the prognosis significantly.     

Immunoglobulin binding factor: A new tumor marker for prostatic tumors

Human seminal plasma contains an immunoglobulin gamma binding factor (IgBF) with an estimated molecular weight of 16 kD under reducing condition. IgBF was detected only in the prostate, including benign prostatic hypertrophy (BPH) and neoplasm. The present study was performed to determine whether IgBF is a useful prostatic marker. Serum IgBF levels were measured in patients with prostatic tumors and in control patients without tumor by radioimmunoassay. Serum prostatic-specific antigen (PSA), the standard prostatic marker, was also determined. Serum IgBF levels in patients with prostate cancer were significantly higher than those in age-matched controls (P < 0.05). Also, patients with BPH tended to have elevated IgBF levels than the controls, although the values were not statistically significant. In control patients, serum IgBF levels increased with advancing age. There was no correlation between serum levels of IgBF and PSA in patients with prostate cancer. Using cut-off level at 28.5 ng/ml (2 S.D. above the mean IgBF level of age-matched control), the sensitivities were 41.2% (7117) for prostate cancer, 23.1% (6/26) for BPH, and 5.6% (1/18) for control patients. In conclusion, serum IgBF is a useful marker in the diagnosis of patients with prostatic tumor, and in evaluating the course of treatment. © 1994 Wiley-Liss, Inc.     

Quantification of prostatic cancer metastatic disease using prostate-specific antigen.

The serum prostate-specific antigen (PSA) of 58 men with benign prostatic hypertrophy (BPH) and 17 men with carcinoma of the prostate (CaP) was correlated with the weight of prostatic tissue resected at transurethral prostatectomy (TURP). A significant correlation was identified between the weight of resected BPH tissue and the serum PSA (p less than or equal to 0.001; r = 0.54). No such correlation was seen in the CaP patients. By arbitrarily dividing the serum PSA by the prostate weight, it was possible to devise an index. This index corrected PSA in relation to prostatic size and unlike PSA in isolation did not differ significantly between normal controls and those with BPH. The index in CaP was significantly greater than that of either controls or BPH (p less than or equal to 0.001). Furthermore the index of metastatic CaP (M1) was significantly higher than that of nonmetastatic disease (MO) (p = 0.05). The higher index found in CaP would seem to be related to the bulk metastatic tumor, either manifest or occult. Comparing the index of CaPs to that found in normal and benign disease (a constant) offers a possible means of estimating the extent of local and metastatic tumor mass.     

Evaluation of prostate-specific antigen in untreated prostatic carcinoma

A study was performed on 290 men to compare the level of serum prostate-specific antigen (PSA) in controls, patients with benign prostatic hyperplasia (BPH) and patients with prostatic cancer. The upper limit of normal was 5.0 micrograms/l as determined in 110 elderly hospitalized males (mean age 62 years) without urological complaints. Of the 106 patients with BPH, 33% had raised values above 5.0 micrograms/l. Values above 10 micrograms/l were found in 18 BPH patients. A positive correlation was found between prostate volume (grams of tissue removed during transurethral resection) and preoperative PSA levels (r = 0.55, n = 106, p less than 0.001). PSA levels above 10 micrograms/l were found in 4% of BPH patients with a prostate volume of less than 20 g (n = 54), in contrast with 45% of patients with a prostate volume above 40 g (n = 20). The sensitivity of this PSA assay (cutoff level 10 micrograms/l) as established in 74 prostate carcinoma patients was 31% for category T0 (n = 13), 56% for category T1-2 (n = 16), 75% for category T3-4 (n = 20) and 100% for category M1 or N1-4 (n = 25). In an earlier study prostatic acid phosphatase (PAP) was measured in these same samples. PSA appeared to be much more sensitive than PAP. Seventeen of the 74 prostatic carcinoma patients (23%) had normal PAP levels but their PSA values were raised above 10 micrograms/l, while in only 2 patients an increased PAP level was combined with a normal PSA.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hormonal predictors of prostate cancer

INTRODUCTION: Androgens are necessary for the development and functioning of the prostate gland. The association of serum testosterone and pituitary hormone levels with prostate cancer development is not completely understood. In this clinical study, we evaluated the role of serum testosterone, free testosterone, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels in predicting prostate cancer risk in patients who had transrectal ultrasonography-guided prostate biopsy with the suspicion of prostate cancer. MATERIAL AND METHODS: A total of 211 patients who were selected to undergo prostatic biopsy due to abnormal digital rectal examination and/or a serum prostate-specific antigen (PSA) level >2.5 ng/ml were included in the study. The patient characteristics of total PSA, free/total PSA ratio, serum total testosterone, free testosterone, free/total testosterone ratio, FSH and LH levels were compared according to the pathological diagnosis. RESULTS: The mean age was 63.91 years (range 44-83) and the mean PSA level was 9.23 ng/ml (range 0.13-50.41) in the whole group. Of 211 patients, 69 (32.7%) were positive for prostate cancer. The patients who were positive for prostate cancer had statistically lower levels of serum total testosterone compared with the patients who were diagnosed as having benign prostatic hyperplasia (BPH; 405 vs. 450.5 ng/dl, respectively; p = 0.013). The serum FSH level was significantly higher in men with prostatic cancer than in men with BPH (7.56 vs. 6.06 mIU/ml, respectively; p = 0.029). No significant differences between men with prostatic cancer and those with BPH were found for serum LH levels. When normal ranges for serum free and total testosterone levels were defined as 9 pg/ml and 300 ng/dl, respectively, patients who had low free testosterone and total testosterone levels had significantly higher cancer detection rates than patients with high serum androgen levels: 40.8% (40/98) versus 25.6% (29/113) (p = 0.021), and 48.6% (18/37) versus 29.3% (51/174), respectively (p = 0.023). After logistic regression analysis, none of the hormones showed a significant difference in predicting the risk of prostate cancer in patients undergoing prostate biopsy with suspicion of the disease. CONCLUSION: Our data suggest that patients diagnosed with prostate cancer have low levels of serum testosterone and high levels of serum FSH compared with the patients with BPH. No support was found for the theory that high levels of testosterone increase prostate cancer risk. Further studies are needed to clarify the relationship between hormones and prostate cancer etiology.     

Osteoporosis and spinal fractures in men with prostate cancer: risk factors and effects of androgen deprivation therapy

PURPOSE: We determined the risk factors for osteoporosis and spinal fractures in men with prostate cancer receiving androgen deprivation therapy. MATERIALS AND METHODS: We performed a retrospective analysis of 87 consecutive men with prostate cancer receiving androgen deprivation therapy referred for evaluation of osteoporosis. Data were comprised of lateral thoracolumbar radiographs, bone densitometry, serum biochemistry and a detailed assessment of osteoporotic risk factors. Multivariate regression analysis was used to determine the major risk factors for osteoporosis and spinal fractures. RESULTS: There were 38 (44%) men who were 74.5 years old with radiographic evidence of spinal fractures. They had an initial mean prostate specific antigen of 52.8 ng/ml and had received androgen deprivation therapy for a mean of 39.6 months (95% confidence interval 28.7 to 50.4). Mean spinal (quantitative computerized tomography t-score -4.2) and femoral neck bone mineral densities (dual energy x-ray absorptiometry t-score -2.1) were significantly lower than in men without spinal fractures (p < 0.001 for all measurements). In the regression analysis the duration of androgen deprivation therapy (p = 0.002), serum 25-hydroxyvitamin D levels (p = 0.003) and a history of alcohol excess (defined as more than 4 standard drinks daily, p = 0.04) were the main determinants of spinal fractures. CONCLUSIONS: Prolonged androgen deprivation therapy, low serum 25-hydroxyvitamin D levels and a history of alcohol excess are important risk factors for osteoporosis and spinal fractures in men with prostate cancer.