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Serum PSA Level (serum + psa_level)

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Value of prostate specific antigen ,1 -antichymotrypsin complex for the detection of prostate cancer in patients with a PSA level of 4.1,10.0ng/mL: Comparison with PSA-related parameters

INTERNATIONAL JOURNAL OF UROLOGY, Issue 11 2001
Hideaki Miyake
Abstract Background: The aim of the present study was to evaluate the usefulness of prostate specific antigen ,1 -antichymotrypsin complex (PSA-ACT) in the differential diagnosis of prostate cancer in patients with a PSA level of 4.1,10.0 ng/mL compared to several PSA- and PSA-ACT-related parameters. Methods: Serum samples were obtained from 103 patients with no evidence of malignancy on biopsy and 29 with histologically confirmed prostate cancer. All patients had pretreatment serum PSA levels between 4.0 and 10.0 ng/mL. The different forms of serum PSA, including total PSA (tPSA), free PSA (fPSA) and PSA-ACT were measured using immunofluorometric techniques with different monoclonal antibodies against PSA and ACT. Furthermore, tPSA and PSA-ACT densities of the whole prostate (PSAD and ACTD, respectively) and the f-to-tPSA and the f-to-PSA-ACT ratios (F/T ratio and F/ACT ratio, respectively) were calculated. Results: The differences between patients with prostate cancer and benign prostatic disease were significant with respect to all six parameters examined in this study. Analysis of receiver operating characteristics revealed that the areas under the curve for PSA-ACT, ACTD and the F/ACT ratio were larger than those for tPSA, PSAD and the F/T ratio, respectively. However, there were no significant differences in discrimination between benign and malignant diseases among these six parameters. Conclusions: In patients who have an intermediate serum PSA level, PSA-ACT and its associated parameters may not be significantly superior in the differential diagnosis between prostate cancer and benign prostatic diseases compared to tPSA and its traditional relatives. [source]

Latest news and product developments

PRESCRIBER, Issue 19 2007
Article first published online: 22 NOV 200
UK data suggest OCs may reduce cancer risk The latest analysis of the RCGP oral contraception (OC) study suggests that oral contraceptives may be associated with an overall reduction in the risk of cancer (Br Med J online: 11 September 2007; doi:10.1136/bmj.39289. 649410.55). The cohort of 46 000 women provided 744 000 woman-years for ever use of an oral contraceptive and 339 000 woman-years of never use. Longer use was associated with increasing risks of cervical (RR 2.73), and pituitary or CNS (RR 5.51) cancers, but decreasing risks of uterine (RR 0.57) and ovarian (RR 0.38) cancers. OC use was also associated with a lower overall risk of colorectal cancers. The overall risk of any cancer was reduced by 12 per cent (RR 0.88). CombAT two-year data Two-year data revealed at the 29th Congress of the Société Internationale d'Urologie in Paris in September show that dutasteride (Avodart) and tamsulosin combination therapy provides significantly improved symptom control in BPH compared with either therapy alone. The Combination therapy with Avodart (dutasteride) and tamsulosin (CombAT) study took over 4800 eligible men (age ,50 years with a prostate volume ,30cc, serum PSA level ,1.5-10ng per ml and IPSS ,12) who received placebo for four weeks before being randomised in a 1:1:1 ratio to either dutasteride monotherapy (0.5mg per day), tamsulosin monotherapy (0.4mg per day) or a combination of both drugs. At two years the primary efficacy end-point was achieved: combination therapy was significantly more effective than either monotherapy, and continuous improvement could be observed throughout the two years. The combination therapy was also well tolerated, although drug-related adverse events were more common with combination therapy (24 per cent) than either monotherapy (dutasteride 18 per cent, tamsulosin 14 per cent). Dutasteride, a 5-, reductase inhibitor, has been shown to be more effective for long-term use in men than tamsulosin, while tamsulosin, an alpha blocker, has been shown to be effective in the short term. CombAT is the first study to demonstrate that the combination therapy of both drugs could lead to greater symptom improvement over time than an alpha blocker alone. Aliskiren - new class of antihypertensive Novartis has introduced aliskiren (Rasilez), the first direct renin inhibitor for the treatment of hypertension. It is likely to be used in combination with other agents but is also licensed as monotherapy. The commonest adverse effect is diarrhoea. At the recommended dose of 150-300mg per day, a month's treatment costs £19.80-£23.80. MHRA updates drug safety advice The balance of benefit and risks from HRT may be more favourable for younger women, the MHRA says in its monthly bulletin, Drug Update (September 2007). GPs considering prescribing HRT should evaluate the potential risks and benefits for each individual, the MHRA says. The bulletin summarises the risks of cardiovascular events and cancers associated with HRT. Cardiovascular risk is a particular concern for women over 60, whose baseline risk is high; although evidence for the safety of HRT in younger women is limited, their baseline risk is lower. Overall, the lowest dose of HRT should be used for the shortest possible time, and HRT should be prescribed to prevent osteoporosis only when alternatives are not suitable. The MHRA also advises in the bulletin that: Individual risk of stroke, breast cancer and endometrial cancer should be considered before prescribing tibolone (Livial). Nasal formulations of desmopressin are no longer indicated for primary nocturnal enuresis; prescribers are reminded to adhere to product guidance on fluid intake. Patients and carers should be warned of the risk of psychiatric effects associated with corticosteroids; symptoms may develop within a few days or weeks in children and adults, and may be more common at higher doses. Patients taking steroids for more than three weeks are reminded not to stop treatment abruptly. A list of questions and answers for patients is available at www.mhra.gov.uk. The use of parenteral B vitamins plus ascorbic acid (Pabrinex) may rarely be associated with severe allergic reactions, but this should not preclude its use for patients who need it. Study claims statin switch may increase CV morbidity Switching patients from atorvastatin (Lipitor) to simvastatin may increase the risk of cardiovascular events, according to a UK study presented at the European Society of Cardiology Congress in Vienna. The analysis, from The Health Improvement Network database, included 11 520 patients taking atorvastatin for at least six months, of whom 2511 were switched to simvastatin. Switching was associated with a 30 per cent increase in the relative risk of cardiovascular events, though absolute figures have not been reported. Patients who were switched were also more likely to discontinue treatment (21 vs 8 per cent of those continuing atorvastatin). Details of the conduct of the study, which will be published in the British Journal of Cardiology, are not available. Glitazones controversy rumbles on New systematic reviews have fuelled the controversy over the cardiac safety of rosiglitazone and pioglitazone. A meta-analysis of four trials involving 14 291 patients and lasting one to four years found that rosiglitazone was associated with a significantly increased risk of myocardial infarction (relative risk, RR, 1.42) and heart failure (RR 2.09) but not cardiovascular mortality (RR 0.90) (J Am Med Assoc 2007;298:1189-95). The second review included 19 trials of pioglitazone involving 16 390 patients, with follow-up from four months to 3.5 years. Pioglitazone was associated with a lower risk of composite events (death, myocardial infarction, stroke; hazard ratio, HR, 0.82) but an increased risk of serious heart failure (HR 1.41) (J Am Med Assoc 2007;298: 1180-8). Neither review reported significant heterogeneity between the included studies. Another systematic review of eight controlled and cohort studies concluded that metformin is the only antidiabetic drug not associated with an increased risk of harm in patients with diabetes and heart failure (Br Med J Online First 30 August; doi:10.1136/bmj.39314. 620174.80). The Canadian authors found methodological problems with all studies, and concluded that results for sulphonylureas were conflicting due to differences between the studies. Asthma prescribing education Health professionals need more education about rational prescribing for children with asthma, say researchers from Australia (Arch Dis Child online: 4 September 2007; doi: 10. 1136/adc.2007.119834). Analysing trends in asthma medication prescriptions for children in the UK between 2000 and 2006, they found the proportion of steroid inhalers prescribed as combinations increased from 2.7 per cent in 2000 to 25 per cent in 2006. The authors say this excessive increase is inconsistent with guidance that steroid-only inhalers should be the mainstay for most people with asthma. Copyright © 2007 Wiley Interface Ltd [source]

The impact of HMG-CoA reductase therapy on serum PSA,

THE PROSTATE, Issue 6 2010
David J. Mener
Abstract BACKGROUND 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase inhibitors, otherwise known as statins, inhibit the enzyme that controls the conversion of HMG-CoA to mevalonate, a precursor for cholesterol. Statins may be important to prostate cancer biology by inhibiting cell growth, inflammation, and oxidative stress. The purpose of this study was to assess the influence of statin therapy on serum prostate-specific antigen (PSA) levels. METHODS The computerized medical records at the University of Rochester Medical Center were used to identify men who filled statin prescriptions between May 31st, 2008 and September 30th, 2008. Men with at least one PSA assay performed within 2 years before and at least one PSA assay performed within 1 year after starting a statin medication were included. The primary endpoint was the change in PSA concentration computed as the difference between PSA levels before and after starting a statin medication. Paired t -tests were used to analyze the mean differences in PSA values. RESULTS A total of 962 patients were identified. The mean difference in serum PSA level after statin administration was ,0.29,ng/ml (,8.04%). Subgroup analyses for mean PSA concentration change before and after statin administration by age group revealed: 50,59 years old (,0.1609, 95% CI: ,0.2444, ,0.0775, P,<,0.0002), 60,69 years old (,0.3393, 95% CI: ,0.4641, ,0.2145, P,<,0.0001), and >70 years old (,0.351, 95% CI: ,0.490, ,0.212, P,<,0.0001). CONCLUSIONS These observations suggest a statistically significant reduction in serum PSA level that is associated with the onset of statin therapy. Prostate 70: 608,615, 2010. © 2009 Wiley-Liss, Inc. [source]

Metastasis suppressor gene Raf kinase inhibitor protein (RKIP) is a novel prognostic marker in prostate cancer

THE PROSTATE, Issue 3 2006
Zheng Fu
Abstract BACKGROUND Diminished expression of Raf kinase inhibitor protein (RKIP), an inhibitor of the Raf signaling cascade, promotes prostate cancer (PCa) metastasis in a murine model, suggesting that it is a metastasis suppressor gene. However, the prognostic significance of RKIP expression and its association with metastasis in PCa patients is unknown. METHODS To investigate RKIP protein expression is a prognostic marker in PCa we performed immunohistochemical staining for RKIP expression in tissue microarrays consisting of 758 non-neoplastic prostate tissues, primary tumors and metastases from 134 PCa patients. The Cox proportional-hazards model was used to adjust for covariates including Gleason score, tumor volume, tumor weight, clinical stage, digital rectal exam findings, serum PSA level and surgical margins. RESULTS RKIP expression was low in approximately 5%, 48%, and 89%of non-neoplastic prostate, primary tumors and metastases, respectively. Low RKIP expression in primary tumors was a strong positive predictive factor for PCa recurrence based on PSA levels. In patients whose primary tumors expressed high RKIP levels, the 7-year PSA recurrence rate was <,10%; whereas in patients with tumors with low RKIP expression the recurrence rate was 50% (P,<,0.001). Multivariate analysis revealed RKIP was an independent prognostic factor (P,<,0.001). CONCLUSION In contrast to increased expression of pro-tumorigenic genes, these results demonstrate decreased protein expression of a gene, for example, RKIP, can serve as a prognostic marker in PCa patients. © 2005 Wiley-Liss, Inc. [source]

A pretreatment nomogram predicting biochemical failure after salvage cryotherapy for locally recurrent prostate cancer

BJU INTERNATIONAL, Issue 2 2010
Philippe E. Spiess
Study Type , Prognosis (retrospective cohort) Level of Evidence 2b OBJECTIVE To gather a pooled database from six tertiary-care referral centres using salvage cryotherapy (SC) for locally recurrent prostate cancer, and develop a pretreatment nomogram allowing a prediction of the probability of biochemical failure after SC, based on pretreatment clinical variables. PATIENTS AND METHODS We retrospectively analysed 797 men treated at six tertiary-care referral centres with SC for locally recurrent disease after primary radiotherapy with curative intent. The median duration of follow-up from the time of SC to the date of last contact was 3.4 years. The primary study endpoint was biochemical failure, defined as a serum prostate-specific antigen (PSA) level after SC of >0.5 ng/mL. RESULTS Overall, the rate of biochemical failure was 66% with a median of 3.4 years of follow-up. A logistic regression model was used to predict biochemical failure. Covariates included serum PSA level at diagnosis, initial clinical T stage, and initial biopsy Gleason score. On the basis of these results, a pretreatment nomogram was developed which can be used to help select patients best suited for SC. Our pretreatment nomogram was internally validated using 500 bootstrap samples, with the concordance index of the model being 0.70. CONCLUSION A pretreatment nomogram based on several diagnostic variables (serum PSA level at diagnosis, biopsy Gleason grade, and initial clinical T stage) was developed and might allow the selection of ideal candidates for SC. [source]

Stage migration in localized prostate cancer has no effect on the post-radical prostatectomy Kattan nomogram

BJU INTERNATIONAL, Issue 5 2010
Ruban Thanigasalam
Study Type , Prognosis (case series) Level of Evidence 4 OBJECTIVE To investigate the effect of prostate-specific antigen (PSA) testing on stage migration in an Australian population, and its consequences on the prognostic accuracy of the post-radical prostatectomy (RP) Kattan nomogram, as in North America widespread PSA testing has resulted in prostate cancer stage migration, questioning the utility of prognostic nomograms in this setting. PATIENTS AND METHODS The study comprised 1008 men who had consecutive RP for localized prostate cancer between 1991 and 2001 at one institution. Two groups were assessed, i.e. those treated in 1991,96 (group 1, the early PSA era), and 1997,2001 (group 2, the contemporary PSA era). Differences in clinicopathological features between the groups were analysed by chi-squared testing and survival modelling. Individual patient data were entered into the post-RP Kattan nomogram and the efficacy assessed by receiver- operating characteristic curve analysis. RESULTS Patients in group 2 had lower pathological stage disease (P = 0.01) and fewer cancers with Gleason score ,8 (P < 0.001) than group 1. Multivariate analysis identified preoperative serum PSA level (P < 0.01) and Gleason score (P < 0.01) as strong predictors of biochemical relapse in both groups. In group 2 pathological stage was not significant, but margin involvement became highly significant (P = 0.004). There was no difference in the predictive accuracy of the Kattan nomogram between the groups (P = 0.253). CONCLUSIONS These findings show a downward stage migration towards organ-confined disease after the introduction of widespread PSA testing in an Australian cohort. Despite this, the Kattan nomogram remains a robust prognostic tool in clinical practice. [source]

Ductal adenocarcinoma of the prostate diagnosed on transurethral biopsy or resection is not always indicative of aggressive disease: implications for clinical management

BJU INTERNATIONAL, Issue 4 2010
Hakan Aydin
Study Type , Prognosis (case series) Level of Evidence 4 OBJECTIVE To report the clinicopathological characteristics of 23 cases of ductal adenocarcinoma of the prostate (DCP) and discuss the implications for clinical management, as DCP is considered an aggressive subtype of prostate adenocarcinoma (PA). PATIENTS AND METHODS The presence of DCP in transrectal ultrasonography-guided prostate biopsy (TRUSB) is associated with adverse pathological findings at radical prostatectomy (RP) and clinical outcomes, and the significance of detecting DCP initially in transurethral biopsy (UB) or transurethral resection (TURP) in the present era of screening with prostate-specific antigen (PSA) is unclear. The study included 23 cases of pure DCP without acinar PA diagnosed on UB or TURP. Demographic information, serum PSA level, follow-up surgical procedures (RP, TURP or TRUSB) and outcome data were collected. RESULTS The mean age of the men was 67.5 years and the mean PSA level before the procedure was 12.5 ng/mL; 14 cases were detected on UB and nine were diagnosed on TURP. The mean (range) follow-up was 4 (1,23) months after the initial procedure. In all, 21 (89%) patients had DCP or PA in follow-up procedures. Two (11%) patients had no residual cancer, one on RP and the other on two repeat TURPs. DCP or PA was found in 12 RP cases; four patients had Gleason score 7 PA, three of which were organ-confined, and eight had Gleason score ,8 PA. Extraprostatic extension, seminal vesicle invasion and regional lymph node metastasis were present in seven, six and two cases, respectively. CONCLUSIONS Most DCP diagnosed on UB or TURP in this contemporary series was associated with aggressive PA, but a subset presented as a small periurethral tumour with no concomitant acinar PA, and was eradicated by the initial biopsy/TURP alone. We recommend that patients with a diagnosis of DCP on UB or TURP undergo follow-up TURP and TRUSB before radical surgery is offered. [source]

S-allylcysteine, a water-soluble garlic derivative, suppresses the growth of a human androgen-independent prostate cancer xenograft, CWR22R, under in vivo conditions

BJU INTERNATIONAL, Issue 4 2007
Qingjun Chu
OBJECTIVE To evaluate the effect of S-allylcysteine (SAC) on CWR22R, a human androgen-independent (AI) prostate cancer xenograft, in nude mice. Despite extensive research worldwide there is no effective way to control the growth of prostate cancer, and we previously reported that SAC and S-allylmercaptocysteine (SAMC), two water-soluble derivatives of garlic, inhibit cancer cell invasion through restoration of E-cadherin expression in vitro. MATERIALS AND METHODS The effects of SAC on tumour cell proliferation markers such as Ki-67 and proliferating cell nuclear antigen, and apoptotic regulators including Bcl-2 and cleaved caspase-3, were assessed by immunohistochemical staining. The inhibitory effects of SAC on prostate cancer invasion was examined by immunoreactivity of E-cadherin and its binding proteins ,, , and ,-catenins. The serum prostate-specific antigen (PSA) level at three different times (initiation, middle and end of treatment) and toxicity of SAC on several organs after treatment were assessed. RESULTS Treatment with SAC resulted in inhibition of the growth of CWR22R, with no detectable toxic effect on nude mice. The SAC-induced growth reduction was correlated with a concurrent reduction in serum PSA level and proliferation rate of xenografts, together with an inhibition of invasion through the restoration of E-cadherin and ,-catenin expression. Furthermore, the apoptotic rate of SAC-treated tumours increased together with a decrease in Bcl-2 and increase in cleaved caspase-3. CONCLUSION These results suggest that this garlic-derived compound might be a potential therapeutic agent for suppressing AI prostate cancer. [source]

Significance of micrometastases in pelvic lymph nodes detected by real-time reverse transcriptase polymerase chain reaction in patients with clinically localized prostate cancer undergoing radical prostatectomy after neoadjuvant hormonal therapy

BJU INTERNATIONAL, Issue 2 2007
Hideaki Miyake
OBJECTIVE To clarify the significance of micrometastases in pelvic lymph nodes in patients treated by radical prostatectomy (RP) for prostate cancer after neoadjuvant hormonal therapy (NHT). PATIENTS AND METHODS The study included 52 patients with clinically localized prostate cancer who received NHT followed by RP. The expression of prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSMA) in 989 lymph nodes isolated from the 52 patients were assessed by a fully quantitative real-time reverse-transcriptase polymerase chain reaction (RT-PCR). We regarded specimens in which either PSA or PSMA mRNA were positive as showing the ,presence of micrometastasis'. Lymph node specimens were also stained immunohistochemically with an antibody against PSA. RESULTS Pathological examinations detected tumour cells in 11 lymph nodes from four patients, and real-time RT-PCR further identified micrometastasis in 40 lymph nodes from 19 patients with no pathological evidence of nodal involvement. The presence of micrometastatic cancer cells was confirmed by immunohistochemical staining in 19 lymph nodes from 11 patients with pathologically negative nodes. The presence of micrometastases was significantly associated with other conventional prognostic variables, including the pretreatment serum PSA level, biopsy Gleason score and surgical margin status. The biochemical recurrence-free survival rate in patients with no micrometastasis was significantly higher than that in those with micrometastasis. Furthermore, multivariate analysis identified the presence of micrometastasis as an independent factor predicting biochemical recurrence. CONCLUSIONS Although residual foci of atrophic prostate cancer cells in resected lymph nodes after NHT can be difficult to diagnose by routine pathological examination, the present results show the usefulness of quantitative real-time RT-PCR targeting PSA and PSMA genes for detecting micrometastatic tumour foci in pelvic lymph nodes from patients with localized prostate cancer treated by NHT followed by RP. Furthermore, the present findings suggest that micrometastases in pelvic lymph nodes might be, at least partly, important in the development of biochemical recurrence in some patients undergoing RP after NHT. [source]

Features and preliminary results of the Dutch centre of the ERSPC (Rotterdam, the Netherlands)

BJU INTERNATIONAL, Issue 2003
M.J. Roobol
OBJECTIVE To describe the preliminary results of the Dutch section of a large multicentre study of screening for prostate cancer, the European Randomized study of Screening for Prostate Cancer (ERSPC), initiated in the Netherlands and Belgium in 1991. MATERIALS AND METHODS After a series of five pilot studies which started in 1991, full-capacity screening started in 1994 with the use of a serum prostate-specific antigen (PSA) determination, a digital rectal examination (DRE) and transrectal ultrasonography (TRUS) as screening tests. Depending on the results and the screening protocol used, men were referred for further examination by sextant biopsies (extended with a seventh biopsy if TRUS showed abnormality). The protocols used, efficiency of the different screening tests, number of cancers detected in the pilot studies, initial screening round and preliminary results of the second screening round are described. RESULTS After the pilot studies it became clear that a study of prostate cancer screening was feasible in the Rotterdam area. The screening protocol was workable and the recruitment rate acceptable (39.5%). An inventory of the population registries of Rotterdam and surrounding municipalities, and the known recruitment rate, made it clear that a contribution of 40 000 men (aged 55,74 years) from the Dutch centre to the ERSPC was feasible. The initial screening round started in December 1993 and lasted until December 1999 (protocol 5,10). In all, 42 376 men were randomized and 1014 cancers detected (5.1%). During this screening the protocol was simplified. After evaluating the different screening tests abnormal results of the DRE and TRUS were omitted as an indication for a sextant biopsy. Only a serum PSA level of , 3.0 ng/mL is now used as the indication. The second screening round started in December 1997 and continues. To December 2002, 9920 men were screened for the second time, 4 years after their initial screening visit. To date 446 cancers have been detected (4.5%); this round will last to December 2003. Further evaluation of the screening regimen and characteristics of the cancers detected are constantly assessed within the Dutch ERSPC. Meanwhile a third screening round has also been initiated, which will last to December 2007. CONCLUSION A prostate cancer screening study of the projected magnitude is feasible in Rotterdam; the recruitment rate is acceptable and the screening tests well tolerated. The study has generated many scientific publications and will be of great value in determining whether prostate cancer screening should be part of general healthcare. [source]

Locally advanced prostate cancer,biochemical results from a prospective phase II study of intermittent androgen suppression for men with evidence of prostate-specific antigen recurrence after radiotherapy

CANCER, Issue 5 2007
Nicholas Bruchovsky MD
Abstract BACKGROUND. Biochemical results from a prospective Phase II trial of intermittent androgen suppression for recurrent prostate cancer after radiotherapy were analyzed for correlations to the onset of hormone-refractory disease. METHODS. Patients with histologically confirmed adenocarcinoma of the prostate and a rising serum prostate-specific antigen (PSA) level after external beam irradiation of the prostate were treated intermittently with a 36-week course of cyproterone acetate and leuprolide acetate. Then, patients were stratified according to their serum PSA range at the start of each cycle and were followed with further biochemical testing until disease progression was evident. RESULTS. The mean PSA reduction was 95.2% irrespective of stratification group. A baseline serum PSA level <10 ,g/L and a serum PSA nadir ,0.2 ,g/L were associated with the longest time off treatment. The overall mean nadir PSA value in the progression group at 1.40 ± 0.19 ,g/L was 2.6-fold greater than the value of 0.55 ± 0.88 ,g/L in the no-progression group (P = .0002). Recovery of serum testosterone to a level of ,7.5 nmol/L was observed in 75%, 50%, 40%, and 30% of men in Cycles 1 to 4, respectively, and was sufficient to normalize the level of hemoglobin in each cycle, which dropped by an average of 10.8 g/L during treatment (P < .0001). CONCLUSIONS. The length of the off-treatment interval during cyclic androgen withdrawal therapy was related inversely to baseline and nadir levels of serum PSA. Nadir PSA was a powerful predictor of early progression to androgen independence. Cancer 2007 © 2007 American Cancer Society. [source]

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

CANCER, Issue 2 2002
Anthony V. D'Amico M.D., Ph.D.
Abstract 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 , 10 ng/mL, and a Gleason score , 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 , 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 , 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. [See editorials on pages 211,4 and 215,8, this issue. Cancer 2002;95:281,6. © 2002 American Cancer Society. DOI 10.1002/cncr.10657 [source]

Expression of prostate-specific antigen and androgen receptor in extramammary Paget's disease and carcinoma

CLINICAL & EXPERIMENTAL DERMATOLOGY, Issue 1 2007
N. Inoguchi
Summary Prostate-specific antigen (PSA) is a kallikrein-like serine proteinase (human kallikrein 3) produced by epithelial cells of both benign and malignant prostate tissue. In this study, PSA expression was histologically examined in tissue specimens from 34 patients with extramammary Paget's disease (EPD; 31 cases) and extramammary Paget's carcinoma (EPC; three cases), but no associated prostate carcinoma. Tumour cells positive for PSA were found in 17 of the 34 cases. Based on this finding, we examined serum PSA level in the three EPC cases. A high level of serum PSA was observed in one case of EPC, which was correlated with disease progression. Because some reports suggest that 50,80% cases of EPD/EPC express androgen receptor (AR), we also examined expression of AR. Immunohistological staining showed correlation of PSA and AR in expression. These results suggest that PSA and the androgen signalling pathway may be involved in the pathogenesis of EPD. [source]

Value of prostate specific antigen ,1 -antichymotrypsin complex for the detection of prostate cancer in patients with a PSA level of 4.1,10.0ng/mL: Comparison with PSA-related parameters

Serum prostate-specific antigen levels reflect the androgen milieu in patients with localized prostate cancer receiving androgen deprivation therapy: Tumor malignant potential and androgen milieu,,

THE PROSTATE, Issue 13 2010
Itsuhiro Takizawa
Abstract BACKGROUND Although androgen deprivation therapy (ADT) has a marked impact on the androgen milieu in vivo and outcomes of prostate cancer (PCa), it remains unclear which parameters reflect the androgen milieu during ADT or whether the milieu is associated with PCa aggressiveness. METHODS Seventy-two patients with localized PCa were prospectively studied based on their blood samples before and after ADT for 6 months. Serum androgens and related values were measured. RESULTS Before ADT, there was no correlation between the serum prostate-specific antigen (PSA) and androgen levels. After ADT, the serum PSA levels were correlated with each level of serum testosterone, dihydrotestosterone, androstenedione, dehydroepiandrosterone-sulfate (DHEA-S), and 3alpha-diol G (P,<,0.010 in all). Before ADT, patients with Gleason score of ,8 were likely to have lower serum testosterone levels than those with Gleason score of ,6 (P,=,0.058). After ADT, conversely, the testosterone levels in patients with Gleason score of ,8 appeared to be higher than in those with Gleason score of ,6 (P,=,0.060). The serum DHEA-S level was correlated with Gleason score before and after ADT (P,=,0.050 and P,=,0.040, respectively). CONCLUSIONS The serum PSA levels well reflect the androgen milieu in localized PCa patients receiving ADT, which can be explained by the Saturation Model and disease control. The androgen milieu in men with high Gleason score PCa is probably less affected by conventional ADT than that in men with low score cancer, which was suggested to be associated with adrenal androgen levels. Prostate 70: 1395,1401, 2010. © 2010 Wiley-Liss, Inc. [source]

Predictive value of PCA3 in urinary sediments in determining clinico-pathological characteristics of prostate cancer,

THE PROSTATE, Issue 1 2010
Daphne Hessels
Abstract PURPOSE PCA3 urine tests have shown to improve the specificity in prostate cancer (PCa) diagnosis, and have thus the potential to reduce the number of unnecessary prostate biopsies and to predict repeat biopsy outcomes. In this study, PCA3 was correlated with clinical stage, biopsy Gleason score (GS), radical prostatectomy GS, tumor volume, and pathological stage to assess its potential as predictor of PCa aggressiveness. METHODS In this study, 351 men admitted for prostate biopsies based on serum PSA levels >3,ng/ml, an abnormal DRE, and/or a family history of PCa were included. Post-DRE urinary sediments from 336 men were tested using a transcription-mediated amplification-based PCA3 test, and assay results were correlated with clinical stage and biopsy GS. In a sub-cohort of 70 men who underwent radical prostatectomy, the PCA3 values were correlated to their radical prostatectomy GS, tumor volume, and pathological stage. RESULTS In this patient cohort we could not find a correlation between clinical stage, biopsy GS, radical prostatectomy GS, tumor volume, and pathological stage. CONCLUSIONS The predictive value of PCA3 for PCa aggressiveness features as reported in earlier studies cannot be confirmed in our study. Experimental differences (urine sediments vs. whole urine) and cohort may explain this. The exact place of PCA3 as prognostic test for PCa remains the subject of investigation. Prostate 70: 10,16, 2010. © 2009 Wiley-Liss, Inc. [source]

In vivo real-time imaging of TGF-,-induced transcriptional activation of the RANK ligand gene promoter in intraosseous prostate cancer

THE PROSTATE, Issue 4 2004
Jian Zhang
Abstract BACKGROUND Current animal models of prostate cancer (CaP) bone metastasis do not allow measurement of either tumor growth in bone over time or activation of gene promoters in intraosseous tumors. To develop these methods, we used bioluminescent imaging (BLI) to determine if expression of receptor activator of NF-,B ligand (RANKL), a pro-osteoclastogenic factor that promotes CaP bone metastases, is modulated by the bone matrix protein transforming growth factor-, (TGF-,) in vivo. METHODS C4-2B human CaP cells were treated with TGF-, in vitro and RANKL mRNA and protein production were measured by polymerase chain reaction (PCR) and ELISA, respectively. Then C4-2B cells stably transfected with the RANKL promoter driving luciferase (lux) were injected intra-tibially into severe combined immundeficient (SCID) mice. Tumors were subjected to BLI every 2 weeks for 6 weeks and serum prostate specific antigen (PSA) was measured using ELISA. Vehicle (V), 1,25 dihydroxyvitamin D (VitD), or TGF-, was administered to mice with established tumors and BLI to measure RANKL promoter activity was performed. Tumors were then subjected to immunohistochemistry for lux and assayed for RANKL mRNA levels. RESULTS TGF-, induced RANKL protein and mRNA expression and activated the RANKL promoter activity in a dose-dependent manner in vitro. BLI demonstrated an increase in intraosseous tumor size over time, which correlated with serum PSA levels. Administration of TGF-, and VitD to mice with established intraosseous tumors increased lux activity compared to V. Intratibial tumor RANKL mRNA expression paralleled the increased promoter activity. Immunohistochemistry confirmed the presence of lux in the intraosseous tumors. CONCLUSIONS These results demonstrate the ability to measure intraosseous tumor growth over time and gene promoter activation in an established intraosseous tumor in vivo and also demonstrate that TGF-, induces activates the RANKL promoter. These results provide a novel method to explore the biology of CaP bone metastases. © 2004 Wiley-Liss, Inc. [source]

Stat3 activation in prostatic carcinomas

THE PROSTATE, Issue 4 2002
Rajiv Dhir
Abstract BACKGROUND Activated Stat3 is found in various types of immortal cell lines and cancers. We and others have previously demonstrated that Stat3 is constitutively activated in rat and human prostate cancer cell lines, and that Stat3 activation is involved in IL-6-mediated signaling transduction in prostate cancer cells. The aim of this study is to examine quantitative Stat3 activity in benign and malignant human prostate tissues and analyze the association between Stat3 activity levels and the clinical and pathologic parameters. METHODS Stat3 activity levels were analyzed in a total of 104 human primary prostate tissues using electromobility shift assay and immunohistochemical staining for phosphorylated Stat3. The tissue samples used were 42 prostate carcinomas, 42 matched normal prostate tissues from patients with prostatic adenocarcinoma (normal adjacent to tumor), and 20 normal prostate tissues from organ donors. RESULTS Significantly higher levels of constitutive Stat3 activity were detected in both prostate carcinomas and the matched normal prostate tissues adjacent to tumors compared to the normal prostates from donors without prostate cancer. There was no significant difference of Stat3 activity in foci of tumor and normal prostate tissue adjacent to tumor. No correlation was seen between Stat3 activity and Gleason grade or serum PSA levels in samples from prostate carcinomas. CONCLUSIONS These results indicate that Stat3 is constitutively activated in prostate cancer. The high level of Stat3 activity in both the prostate carcinomas and the normal prostate tissues adjacent to tumors suggests that Stat3 activation may occur before detectable histological alterations of the prostate. Prostate 51: 241,246, 2002. © 2002 Wiley-Liss, Inc. [source]

Age-specific reference levels of serum prostate-specific antigen and prostate volume in healthy Arab men

BJU INTERNATIONAL, Issue 3 2005
Elijah O. Kehinde
OBJECTIVE To determine age-specific reference ranges for serum prostate-specific antigen (PSA) concentration and prostate volumes in a population of healthy Arab men. SUBJECTS AND METHODS Blood samples were taken from 396 healthy Arab men (from Kuwait and Oman) aged 15,79 years and from across the social spectrum. Men aged >40 years had a digital rectal examination and transrectal ultrasonography of the prostate to determine prostate volume. The serum PSA level was measured using commercial kits, and age-specific ranges for PSA levels and prostate volume determined. RESULTS The serum PSA ranges (ng/mL) for each age range in Arab men were: 40,49 years, 0,0.9; 60,69, 0,2.7; 70,79, 0,5.5 ng/mL; the respective prostate volumes were 8,22, 9,30 and 10,33 mL. The serum PSA level and prostate volume correlated with age (P < 0.001). Arab men had lower serum PSA levels and prostate volumes than those reported for Caucasians, but similar to those reported for Asians (Japanese and Chinese). CONCLUSION These results indicate that Arab men have lower PSA levels and prostate volumes than Caucasians. The levels are slightly lower than those reported in the Japanese and, as in the Japanese, low PSA levels and small prostate volumes might be related to the low incidence of clinical prostate cancer in Arab men. [source]

Transrectal power Doppler imaging in the detection of prostate cancer

BJU INTERNATIONAL, Issue 9 2000
K. Okihara
Objectives To evaluate the clinical utility of transrectal power Doppler imaging (PDI) of the prostate for detecting prostate cancer in patients with abnormally high serum levels of prostate specific antigen (PSA). Patients and methods Patients (107) with abnormally high serum PSA levels were assessed using a digital rectal examination (DRE), transrectal ultrasonography (TRUS) and PDI. Any hypervascular lesion on PDI was graded on a scale of 0,3, where grade 1,3 was considered positive and grade 0 negative. Patients were then diagnosed by prostatic needle biopsy and the results compared with the other detection methods. Results Needle biopsy confirmed prostate cancer in 41 (24%) of the 170 patients. PDI was positive in 68, of whom 40 (59%) had prostate cancer; all those but one having prostate cancer were positive on PDI. Thus, PDI had a high sensitivity of 98% (40/41) and a negative predictive value of 99% (101/102). PDI could have saved a significant number of patients from undergoing unnecessary biopsies, compared with DRE and TRUS (P < 0.001). Conclusion The use of PDI in detecting prostate cancer might reduce the number of unnecessary needle biopsies of the prostate in patients with abnormally high serum PSA levels. [source]