Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Prostatism”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,117 records · Page 62Linked to original sources
PubMed1994

Preoperative serum prostate-specific antigen and Gleason grade as predictors of pathologic stage in clinically organ confined prostate cancer: implications for the choice of primary treatment.

PURPOSE: Despite careful preoperative staging, approximately 50% of patients who undergo radical prostatectomy for clinical stage A2 (T1b-c) and B (T2) prostate cancer are found to have pathologic stage C (T3-4) or D (N1) disease. This study investigates whether preoperative serum prostate specific antigen (PSA) and Gleason grade predict pathologic stage among patients with clinically organ confined prostate cancer. METHODS: The records of all 63 patients who underwent attempted pelvic lymphadenectomy and radical prostatectomy for adenocarcinoma of the prostate at our institution in 1990-91 were retrospectively reviewed. RESULTS: Patients with a preoperative serum PSA of 12.5 ng/mL or greater had an 81% incidence of pathologic upstaging to stage C (T3-4) or D (N1) compared with 38% for patients with a PSA less than 12.5 (p = 0.0015). The incidence of various pathologic findings for prostate specific antigen > or = 12.5 vs. prostate specific antigen < 12.5 was as follows: seminal vesicle involvement 29% vs. 5% (p = 0.0186), lymph node metastases 24% vs. 0% (p = 0.0029), capsular penetration 71% vs. 38% (p = 0.0424), and positive margins 47% vs. 36% (p = 0.56). None (0/3) of the patients with Gleason grade 4 or less were pathologically upstaged compared with 49% (24/49) of patients with grade 5-7 tumors (p = 0.15) and 82% (9/11) of patients with grade 8 or higher cancers (p = 0.0474, grade 5-7 vs. 8-10). Within the group of patients with Gleason grade 5-7, a prostate specific antigen of 12.5 ng/mL or greater predicted an 79% rate of upstaging compared with 37% for patients with prostate specific antigen less than 12.5 (p = 0.0098). CONCLUSION: Patients with clinical Stage A2 (T1b-c) or B (T2) prostate cancer who have Gleason grade 8-10 tumors and those patients with Gleason grade 5-7 tumors with a preoperative serum prostate specific antigen of 12.5 ng/mL or higher have a high incidence of pathologic upstaging. These patients should be preferentially treated with external beam radiation in most cases.

Adenocarcinoma↗
PubMedDate not supplied

Associations between polymorphisms in the steroid 5-alpha reductase type II (SRD5A2) gene and benign prostatic hyperplasia and prostate cancer.

The prostate gland is an androgen-dependent, and polymorphisms in androgen synthesis gene steroid 5-alpha reductase type II (SRD5A2) may be associated with benign prostatic hyperplasia (BPH) and prostate cancer. We evaluated the association between 3 polymorphisms in the SRD5A2 gene (2 single nucleotide polymorphism: alanine-49 to threonine [A49T] and valine-89 to leucine [V89L], and a (TA)n dinucleotide repeat in the 3' untranslated region), and BPH and prostate cancer within a multiethnic population. Men between 60 and 86 years of age were recruited from annual prostate cancer screening programs and from a large urology clinic. Unconditional logistic regression was used to compute odds ratios (OR) and 95% confidence intervals (95% CI). We genotyped 606 men (412 Hispanic, 98 Caucasian, 73 African-American, and 23 Asian), of whom 100 had prostate cancer, 393 had BPH (280 symptomatic and 113 asymptomatic), and 113 had normal prostates. Overall, the V89L variant was associated with prostate cancer; the OR for men with the leucine-leucine (LL) genotype compared to men with the valine-valine (VV) genotype was 4.47 (95% CI, 1.24-16.18). This association was stronger in Hispanics (OR=7.26; 95% CI: 1.49-35.47). Although V89L was nonsignificantly associated with BPH in overall population, BPH risk increased significantly with the number of L alleles in Hispanics (P for trend=0.03). Prostate cancer and BPH were not associated with the alanine-49 to threonine single nucleotide polymorphism and the (TA)n repeat. These results suggest that the SRD5A2 gene may play an important role in both BPH and prostate cancer.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1999

Proliferative inflammatory atrophy of the prostate: implications for prostatic carcinogenesis.

Proliferation in the setting of longstanding chronic inflammation appears to predispose to carcinoma in the liver, large bowel, urinary bladder, and gastric mucosa. Focal prostatic atrophy, which is associated with chronic inflammation, is highly proliferative (Ruska et al, Am J Surg Pathol 1998, 22:1073-1077); thus the focus of this study was to more fully characterize the phenotype of the atrophic cells to assess the feasibility of the proposal that they may be targets of neoplastic transformation. The pi-class glutathione S-transferase (GSTP1), a carcinogen-detoxifying enzyme, is not expressed in >90% of prostate carcinomas (CaPs). GSTP1 promoter hypermethylation, which appears to permanently silence transcription, is the most frequently detected genomic alteration in CaP (Lee et al, Proc Natl Acad Sci USA 1994, 91:11733-11737; >90% of cases). In high-grade prostatic intraepithelial neoplasia (PIN), this alteration is present in at least 70% of cases (Brooks et al, Cancer Epidemiol Biomarkers Prev, 1998, 7:531-536). Although normal-appearing prostate secretory cells rarely express GSTP1, they remain capable of expression, inasmuch as GSTP1 promoter hypermethylation is not detected in normal prostate. Fifty-five lesions from paraffin-embedded prostatectomy specimens (n = 42) were stained for GSTP1, using immunohistochemistry. Adjacent sections were stained for p27(Kip1), Ki-67, androgen receptor (AR), prostate-specific antigen (PSA), prostate-specific acid phosphatase (PSAP), Bcl-2, and basal cell-specific cytokeratins (34betaE12). With normal prostate epithelium as the internal standard, staining was scored for each marker in the atrophic epithelium. The lesions showed two cell types, basal cells staining positive for 34betaE12, and atrophic secretory-type cells staining weakly negative for 34betaE12. All lesions showed elevated levels of Bcl-2 in many of the secretory-type cells. All lesions had an elevated staining index for the proliferation marker Ki-67 in the secretory layer and decreased expression of p27(Kip1), a finding reminiscent of high-grade PIN (De Marzo et al, Am J Pathol 1998, 153:911-919). Consistent with partial secretory cell differentiation, the luminal cells showed weak to moderate staining for androgen receptor and the secretory proteins PSA and PSAP. All atrophic lesions showed elevated GSTP1 expression in many of the luminal secretory-type cells. Because all lesions are hyperproliferative, are associated with inflammation, and have the distinct morphological appearance recognized as prostatic atrophy, we suggest the term "proliferative inflammatory atrophy" (PIA). Elevated levels of GSTP1 may reflect its inducible nature in secretory cells, possibly in response to increased electrophile or oxidant stress. Elevated Bcl-2 expression may be responsible for the very low apoptotic rate in PIA and is consistent with the conclusion that PIA is a regenerative lesion. We discuss our proposal to integrate the atrophy and high-grade PIN hypotheses of prostate carcinogenesis by suggesting that atrophy may give rise to carcinoma either directly, as previously postulated, or indirectly by first developing into high-grade PIN.

Apoptosis↗
PubMed1998

Induction of prostate apoptosis by doxazosin in benign prostatic hyperplasia.

PURPOSE: The molecular mechanisms underlying the therapeutic effect of the alpha1 blocker, doxazosin, on benign prostatic hyperplasia (BPH) are poorly understood. We evaluated the effect of doxazosin on cell proliferation and apoptosis in the prostatic glandular epithelium and stroma of patients with BPH. MATERIALS AND METHODS: We examined proliferative and apoptotic activities in prostate specimens of 22 men a mean of 65 years old with BPH before and after doxazosin treatment within the normal therapeutic range. Proliferative and apoptotic indexes were determined using Ki-67 nuclear antigen staining and the terminal transferase end labeling assay, respectively. The smooth muscle cell content in prostatic specimens was identified by smooth muscle alpha-actin, and desmin immunoreactivity and apoptotic indexes were correlated with prostatic stromal tissue regression and improvement in BPH symptoms. RESULTS: In response to doxazosin treatment there were no significant changes in the kinetics of cell proliferation in the prostatic epithelial or stromal cell population. Mean pretreatment baseline apoptosis was 1.9 and 1.0% for the epithelial and stromal prostate components, respectively. Mean apoptotic indexes significantly increased after 3 months of doxazosin treatment in the glandular epithelial (6%) and smooth muscle cells (15%). By 12 months after treatment epithelial apoptosis had decreased to constitutive levels, while the apoptotic index of prostatic stroma cells remained high. Doxazosin induced smooth muscle cell apoptosis correlated with prostatic stromal degeneration, decreased alpha-smooth muscle actin expression and improved BPH symptoms. CONCLUSIONS: These findings implicate the induction of prostate apoptosis by doxazosin as a potential molecular mechanism underlying the acute and chronic therapeutic responses of BPH to alpha1 blockade.

Adrenergic alpha-Antagonists↗
PubMed1989

Prostate specific antigen in the diagnosis and treatment of adenocarcinoma of the prostate. III. Radiation treated patients.

Serum prostate specific antigen was determined (Yang polyclonal radioimmunoassay) in 183 men after radiation therapy for adenocarcinoma of the prostate. A total of 163 men had received 7,000 rad external beam radiotherapy and 20 had been implanted with 125iodine seeds. Only 11 per cent of these 183 patients had undetectable prostate specific antigen levels at a mean interval of 5 years since completion of radiotherapy. Prostate specific antigen levels after radiotherapy were directly related to initial clinical stage and Gleason score before treatment. Multiple prostate specific antigen determinations were performed with time in 124 of 183 patients. During year 1 after radiotherapy prostate specific antigen levels were decreasing in 82 per cent of the patients but only 8 per cent continued to decrease beyond year 1. Of 80 patients observed greater than 1 year after completion of radiotherapy 51 per cent had increasing values and 41 per cent had stable values. Increasing prostate specific antigen values after radiotherapy were correlated with progression to metastastic disease and residual cancer on prostate biopsy. Total serum acid phosphatase levels were poorly related to prostate specific antigen levels, were less effective in discriminating patients with metastatic disease and provided no additional information beyond that provided by prostate specific antigen.

Acid Phosphatase↗
PubMed1988

Effect of endocrine treatment on prostatic blood flow in patients with prostatic adenocarcinoma.

Prostatic blood flow in 19 patients with prostatic adenocarcinoma was measured by the hydrogen gas clearance method before and during endocrine treatment. Prostatic volume was reduced to 70 per cent of the pre-treatment volume by 3 months after the beginning of treatment. Prostatic blood flow was remarkably depressed in patients who had never had any treatment of the prostatic carcinoma (22.2 +/- 8.3 ml. per minute per 100 gm.), while prostatic blood flow increased significantly after endocrine treatment (56.3 +/- 21.8 ml. per minute per 100 gm.). It was likely that prostatic blood flow increased as the prostate volume decreased. Final histology of serial prostatic biopsy specimens after endocrine treatment, revealed distinct deterioration of tumor cells and slight stromal hyperplasia compared to the initial pre-treatment biopsy. The stromal-epithelial ratio, which was calculated by computer-assisted image analysis, was markedly increased after endocrine treatment. Our study indicated that endocrine treatment caused a growth-inhibitory effect that was accompanied by increased blood flow in the prostatic carcinoma.

Adenocarcinoma↗
PubMed1984

Decreased prostatic secretory function in canine benign prostatic hyperplasia is not due to decreased levels of muscarinic cholinergic receptors.

The ejaculatory volume and the prostatic secretory capacity (ml. ejaculate per gm. prostate wet weight) were determined for a group of dogs with normal and hyperplastic prostates. The ejaculatory volume and prostatic secretory capacity in dogs with BPH were decreased by 70 per cent and 80 per cent respectively, compared to dogs with normal prostates. Radioligand receptor binding using [3H]N-methylscopolamine, a muscarinic cholinergic antagonist, was performed on a similar group of dogs with normal and hyperplastic prostates. The mean equilibrium dissociation constant for the binding of [3H]N-methylscopolamine to homogenates obtained from normal and hyperplastic prostates was 0.21 nM. and 0.19 nM. respectively, demonstrating that the affinity of the receptor binding sites was not altered by the development of BPH. The tissue density of the muscarinic cholinergic receptors (fmol. per mg. prostate wet weight) and the cellular density of these receptors (fmol. per mg. DNA) were not significantly different in normal and hyperplastic prostates. These data indicate that the dramatic reduction in prostatic secretory capacity associated with canine BPH is not related to changes in the muscarinic cholinergic receptor binding capacity.

Animals↗
PubMed2000

Today men with prostate cancer have larger prostates.

OBJECTIVES: To examine the relationship between prostate size and the method of cancer detection in men with organ-confined prostate cancer, and compare prostate size in men with and without cancer. METHODS: Prostate volume was evaluated in 720 men who had undergone radical prostatectomy for Stage T1c or Stage T2 cancer. Men with Stage T2 cancer were divided into those treated before 1989 (when widespread prostate-specific antigen [PSA] testing began), or not. Gland volume was also examined in 265 men participating in the Baltimore Longitudinal Study of Aging who had no clinical evidence of cancer. Volumes were compared using linear regression to allow for age. RESULTS: Prostate volume in men with Stage T1c cancer was statistically significantly larger than in men with Stage T2 cancer diagnosed in the pre-PSA era after adjusting for age (P = 0.0001), and statistically significantly larger than in men without cancer above age 47 years based on 95% confidence intervals. Prostate volumes in men with Stage T2 cancer diagnosed in the pre-PSA era and in men without cancer were not statistically significantly different. CONCLUSIONS: Prostate volume in men with PSA-detected, organ-confined cancer is larger than in men with palpable organ-confined cancer diagnosed in either the pre-PSA era or PSA era. These discrepancies may reflect a diagnostic bias due to the effect of benign prostatic hyperplasia on serum PSA that results in the selection of men with larger prostates for biopsy.

Adult↗
PubMed2001

DNA-based detection of prostate cancer in urine after prostatic massage.

OBJECTIVES: Promoter hypermethylation of the glutathione-S-transferase P1 (GSTP1) gene is a specific feature of prostate cancer. This epigenetic DNA alteration served as the target for molecular detection of prostate cancer cells in urine sediments after prostatic massage. METHODS: Bisulfite treatment followed by methylation-specific polymerase chain reaction was used to detect GSTP1 promoter hypermethylation in DNA isolated from urine sediments obtained after prostatic massage of men with and without prostate cancer. RESULTS: GSTP1 promoter hypermethylation was demonstrated in the sediments of 1 (2%) of 45 patients diagnosed with benign prostatic hyperplasia, 2 (29%) of 7 patients with prostatic intraepithelial neoplasia, 15 (68%) of 22 patients with early, intracapsular cancer, and 14 (78%) of 18 patients with locally advanced or systemic prostate cancer, resulting in a specificity of 98% and an overall sensitivity of 73% for the detection of prostate cancer. CONCLUSIONS: Urinalysis for GSTP1 promoter hypermethylation constitutes a sensitive and highly specific DNA-based marker for molecular detection of prostate cancer, including early stages.

Adenocarcinoma↗
PubMed1994

Relationship between prostatic epithelial volume and serum prostate-specific antigen levels.

OBJECTIVES: The present study was designed to determine the relationship between serum prostate-specific antigen (PSA) levels and prostatic epithelial volumes. METHODS: Forty-two men between the ages of 50 and 79 years of age with either an abnormal digital rectal examination (DRE) or a serum PSA level > 4 ng/dL underwent transrectal ultrasonography (TRUS) and ultrasound-guided random systematic biopsy of the prostate. The volumes of the peripheral zone (PZ) and transition zone (TZ) were calculated, assuming that the total prostate and TZ are ellipsoidal structures. Six random systematic biopsies were directed into the PZ and four random systematic biopsies were directed into the TZ under ultrasound guidance. Among the 42 patients undergoing prostatic biopsy, adenocarcinoma of the prostate was identified in 21 (50%). Tissue sections obtained from the biopsy specimens of the subjects without histologic evidence of prostate cancer were stained with Mallory trichrome stain, and the percentage area density of epithelium in the biopsy cores was determined using computer-assisted color image analysis. The relationships between serum PSA and total, PZ, and TZ epithelial volumes, and serum PSA and total, PZ, and TZ prostatic volumes were determined using regression analysis. RESULTS: The difference between the mean percentage epithelial density of the PZ (17.79 +/- 1.40%) and TZ (10.32 +/- 0.82%) was statistically significant (p < 0.0001). The mean volumes of epithelium in the PZ and TZ were 4.25 +/- 0.47 cc and 3.39 +/- 0.45 cc, respectively. The p and r2 values for the relationship between serum PSA and total prostatic volume were 0.016 and 0.260, respectively. Statistically significant correlations were also observed between serum PSA levels and TZ epithelial volumes (p = 0.0009; r2 = 0.449) and serum PSA levels and TZ volumes (p = 0.007; r2 = 0.329). Statistically significant correlations were not observed between serum PSA levels and the following parameters: PZ volume, PZ epithelial volume, and total prostatic epithelial volume. CONCLUSIONS: Although the PZ contains a significantly greater area density and absolute volume of epithelium than the TZ, the serum PSA level is most strongly correlated only with the volume of epithelium in the TZ.

Age Factors↗
PubMed1996

Prostate volume predicts outcome of treatment of benign prostatic hyperplasia with finasteride: meta-analysis of randomized clinical trials.

OBJECTIVES: Six randomized clinical trials have compared at least 1 year of 5 mg finasteride to placebo in the treatment of clinical benign prostatic hyperplasia (BPH). The findings for the 2601 men in these trials provide an opportunity to investigate the heterogeneity of the effects seen in the individual studies and to identify pretreatment predictors of outcomes as expressed by symptoms or peak urinary flow rates. METHODS: A formal meta-analysis using an Empirical Bayes approach employed data from all finasteride studies which included the Phase III trials in North America and Internationally, the Prospect, Early Intervention, and SCARP trials, and the Veterans Administration Cooperative Study which compared terazosin, finasteride, and the combination of these two drugs. A pooled analysis was also undertaken on the combined dataset. RESULTS: The effect of finasteride treatment on improvements in total symptom severity, frequency score, and peak urinary flow rate was consistent across all six trials and similar among men with similar prostate volumes at baseline. Symptom severity improved by 1.8 points (95% confidence interval [CI], 0.7 to 2.9) in men with prostate volumes less than 20 cc (n = 72), while the improvement was 2.8 points (95% CI, 2.1 to 3.5) for men with volumes greater than 60 cc (n = 272) on the Quasi-IPSS Scale (range 0 to 30). Similarly, improvements in peak urinary flow rate ranged from 0.89 mL/s (95% CI, -0.05 to 1.83) for men with prostate volumes less than 20 cc to 1.84 mL/s (95% CI, 1.37 to 2.30) in men with volumes greater than 60 cc. The difference in the magnitude of improvement between finasteride and placebo becomes significant (that is, no overlap in 95% CI) for men with a baseline prostate volume assessed by either transrectal ultrasonography or magnetic resonance imaging of greater than 40 cc, which encompasses approximately 50% of the entire population. Baseline prostate volume is a key predictor of treatment outcomes: approximately 80% of the variation in the treatment effects noted between studies could be attributed to differences in mean prostate volumes at baseline. Variation in entry criteria results in large differences in baseline symptom severity status, prostate volume, and consequently apparent inconsistencies in the overall outcomes of these trials. CONCLUSIONS: This meta-analysis suggests that finasteride is most effective in men with large prostates. Men with small prostates may not be suitable candidates for finasteride therapy for BPH. The need for a careful reevaluation of the definitions and terminology used when discussing urination problems is apparent.

Enzyme Inhibitors↗
PubMed1998

Expression of prostatic factors measured by reverse transcription polymerase chain reaction in human papillomavirus type 18 deoxyribonucleic acid immortalized prostate cell lines.

OBJECTIVES: To investigate expression of the prostatic markers prostate-specific antigen (PSA), prostate-specific membrane antigen (PSM), and the androgen receptor (AR) after human papillomavirus (HPV) type 18 deoxyribonucleic acid (DNA) transfection and subsequent immortalization of human prostate epithelial cells. METHODS: Recently, two human prostate epithelial cell lines were established by HPV transformation: PZ-HPV-7, derived from normal peripheral zone (PZ) tissue, and CA-HPV-10, derived from high Gleason grade adenocarcinoma. Expression of PSA was studied by the reverse transcription polymerase chain reaction (RT-PCR), because in preliminary studies using immunocytochemistry and Northern blotting, no PSA expression was found. PSM was analyzed by RT-PCR and nested RT-PCR. These analyses included primary human prostate cell strains. Furthermore, androgen-supplemented methylthiazol tetrazolium (MTT) growth assays were performed and expression of AR was studied by immunocytochemistry. Prostate carcinoma cell lines LNCaP and PC-346C were included as positive controls and breast carcinoma cell line MCF-7 as a negative control. RESULTS: Both cell lines exhibited low levels of RNA for PSA and PSM in comparison with cell lines LNCaP and PC-346C. AR expression by immunocytochemistry was negative using monoclonal antibody F39.4 and polyclonal antibody SP-197. In an androgen-supplemented environment, growth rates of both HPV immortalized cell lines were not stimulated in contrast to LNCaP. CONCLUSIONS: RNA transcripts of PSA and PSM were detected by RT-PCR in HPV immortalized prostate epithelial cell lines PZ-HPV-7 and CA-HPV-10. The expression of prostate-specific markers may further validate the utility of this stepwise transformation model of human prostate carcinogenesis.

Antigens, Surface↗
PubMed2002

Prostate brachytherapy postimplant dosimetry: a comparison of prostate quadrants.

PURPOSE: To investigate postimplant dosimetry for different regions of the prostate gland in patients treated with transperineal 125Iodine brachytherapy implants for low- and intermediate-risk prostate cancer. METHODS AND MATERIALS: Two hundred eighty-four patients treated with permanent interstitial prostate brachytherapy comprised the study population. A nonuniform, urethral-sparing algorithm was used to plan all patients. Prostate contours were outlined on postimplant CT images. Prostate volumes were then divided into four quadrants: anterior-superior quadrant (ASQ), posterior-superior quadrant (PSQ), anterior-inferior quadrant (AIQ), and posterior-inferior quadrant (PIQ). Dose-volume histograms (DVHs) were calculated for the whole prostate and each quadrant. RESULTS: The mean postimplant V(100) +/- 95% confidence (the percent prostate volume encompassed within the isodose surface comprising the prescription dose = 144 Gy) for the ASQ was 78.5 +/- 1.9, which was significantly lower than that of the PSQ, AIQ, and PIQ in which the V(100) plus minus 95% confidence values were 94.9 +/- 0.8, 92.6 +/- 1.2, and 98.7 +/- 0.3, respectively. The mean V(100) +/- 95% confidence for the whole prostate was 90.4 +/- 0.8. Mean values for V(150) and D(90) (the minimum dose in Gy received by 90% of the target volume) for the four quadrants and the whole prostate showed similar results. CONCLUSIONS: Underdosed areas of the planning target volume (PTV), if present, were largely confined to the ASQ, which received a significantly lower dose, on average, compared to the other three quadrants of the prostate.

Aged↗
PubMed2000

Short-course intensity-modulated radiotherapy for localized prostate cancer with daily transabdominal ultrasound localization of the prostate gland.

PURPOSE: To present our initial observations on the clinical feasibility of the technique of short-course intensity-modulated radiotherapy (SCIM-RT) in the treatment of localized prostate cancer coupled with daily transabdominal ultrasound localization of the prostate. The proposed regimen consists of a hypofractionated course delivering 70.0 Gy in 28 fractions. METHODS AND MATERIALS: The treatment data of the first 51 patients treated with SCIM-RT at the Cleveland Clinic Foundation are presented in this report. The technique consisted of intensity-modulated radiotherapy using 5 static fields (anterior, 2 laterals, and 2 anterior obliques). Inverse plans were generated by the Corvus treatment-planning system. The treatment delivery was performed with a Varian Dynamic Multileaf Collimator. The target was the prostate only in patients with low-risk disease (stage T1-T2, pretreatment PSA < or =10, and biopsy Gleason < or =6). The target was the prostate and seminal vesicles in patients with high-risk disease (stage T3 or pretreatment PSA > 10 or biopsy Gleason > or =7). In the Corvus planning system, the margins for the planning target volume (PTV) were 4 mm posteriorly, 8 mm laterally, and 5 mm in all other directions. A total of 70.0 Gy (mean prostate dose approximately 75 Gy) was prescribed in all cases at 2.5 Gy per fraction to be delivered in 28 fractions over 5 1/2 weeks. Prior to treatment delivery, the patients were minimally immobilized on the treatment table, only using lasers and skin marks. The location of the prostate gland was verified daily with the BAT transabdominal ultrasound system and patient position adjustments were performed accordingly. Fifty-one patients completed therapy between October 1998 and May 1999. RESULTS: The dose was prescribed to an isodose line ranging from 82.0% to 90.0% (mean: 87.2%). The range of the individual prostate mean doses was 73.5 to 78.5 Gy (average: 75.3 Gy). The range of the maximum doses was 77.4 to 84.5 Gy (average: 80.2 Gy). The range of the minimum doses was 64.3 to 69.2 Gy (average: 67.5 Gy). The average time for the prostate position verification and alignment of the prostate using the BAT system was 5 minutes. The entire localization/alignment process was performed by the radiation therapists. The daily alignment images were automatically saved and reviewed by the radiation oncologist, a process similar to port film checks. The total treatment (beam-on) time was around 6 minutes using the 5 static intensity-modulated fields. The mean and standard deviation (SD) of bladder volumes irradiated to 50, 60, and 70 Gy were as follows: 24 +/- 11 cc, 16 +/- 8 cc, and 8 +/- 6 cc. The mean and SD of rectal volumes irradiated to 50, 60, and 70 Gy were as follows: 22 +/- 11 cc, 15 +/- 8 cc, and 7 +/- 5 cc. The RTOG acute bladder toxicity scores were as follows: 0 in 3 (6%), 1 in 38 (74%), and 2 in 10 (20%). The RTOG acute rectal toxicity scores for SCIM-RT cases were as follows: 0 in 10 (20%), 1 in 33 (65%), and 2 in 8 (16%). No Grade 3 or 4 acute toxicities were observed. CONCLUSION: The delivery of our proposed hypofractionated-schedule SCIM-RT in combination with daily target localization/alignment with the BAT transabdominal ultrasound system is clinically feasible. It is an alternative method of dose escalation in the treatment of localized prostate cancer. The proposed schedule would significantly increase convenience to patients due to the decrease in overall treatment time. Preliminary acute toxicity results are extremely encouraging. Long-term follow-up is needed to assess late complications and treatment efficacy.

Dose Fractionation, Radiation↗
PubMed2006

Use of the PSA enhancer core element to modulate the expression of prostate- and non-prostate-specific basal promoters in a lentiviral vector context.

Composite promoters combining the prostate-specific antigen (PSA) enhancer core element with promoter elements derived from gene coding for human prostate-specific transglutaminase gene, prostate-specific membrane antigen gene, prostate-specific antigen, rat probasin or phosphoglycerate kinase were characterized for their ability to specifically express the enhanced green fluorescent protein (EGFP) gene in prostate versus non-prostate cancer cell lines when transferred with a human immunodeficiency virus-1-based lentiviral vector. By themselves minimal proximal promoter elements were found to inefficiently promote relevant tissue-specific expression; in all the vectors tested, addition of the PSA enhancer core element markedly improved EGFP expression in LnCaP, a cancer prostate cell line used as a model for prostate cancer. The composite promoter was inactive in HuH7, a hepatocarcinoma cell line used as a model of neighboring non-prostate cancer cells. Among the promoters tested, the combination of the PSA enhancer and the rat probasin promoter showed both high specificity and a strong EGFP expression. Neither a high viral input nor the presence of the cPPT/CTS sequence affected composite promoter behavior. Our data suggest that composite prostate-specific promoters constructed by combining key elements from various promoters can improve and/or confer tissue specific expression in a lentiviral vector context.

Cell Line, Tumor↗
PubMed2000

The short-term prostate-specific antigen velocity before biopsy can be used to predict prostatic histology.

OBJECTIVES: To evaluate whether the short-term prostate-specific antigen (PSA) velocity before biopsy can be used to predict prostatic histology, and to assess the role of a second PSA measurement before prostate biopsy. PATIENTS AND METHODS: The study comprised 197 patients who were referred for transrectal ultrasonography (TRUS) and prostate biopsy. The PSA level was initially measured at the first outpatient assessment; patients with a serum PSA level of < 4 ng/mL and > 50 ng/mL were excluded. Blood samples were taken just before prostate biopsy for the second PSA measurement. The mean interval between the measurements was 2.2 months. The short-term PSA velocity was calculated and correlations between this variable and age, prostate volume and initial PSA levels determined. RESULTS: There was a statistically significant difference between the short-term PSA velocity of patients with benign prostate histology and those with prostate cancer (P < 0.05). The short-term PSA velocity alone had the same diagnostic accuracy as the serum PSA level (area under the receiver-operating characteristic curve 0.612). There was only a weak correlation between the short-term PSA velocity and prostate volume. However, there was no correlation with age and initial PSA level in patients with benign histology. The second PSA measurement had higher specificity without losing sensitivity. CONCLUSION: The short-term PSA velocity estimated before biopsy can be used to predict prostatic histology. By measuring serum PSA 2 months after the first in patients with serum PSA level of 4-10 ng/mL, the number of negative biopsies can be reduced by 17%.

Aged↗
PubMed2003

Problems with prostate specific antigen screening for prostate cancer in the primary healthcare setting in South Africa.

OBJECTIVES: To assess the feasibility of detecting early-stage prostate cancer in the primary healthcare setting, and to investigate whether there is a higher incidence of prostate cancer in Black African men. PATIENTS AND METHODS: The study was a collaboration with registrars in the authors' institutions and primary healthcare centres serving mainly a Black African or mixed ancestry (Coloured) population in the semi-urban Cape Town metropolitan area of South Africa. Men aged 50-70 years attending the clinics were counselled about prostate cancer and invited to have a digital rectal examination (DRE), serum prostate-specific antigen (PSA) assay and transrectal ultrasonography-guided sextant prostate biopsy if the DRE was clinically suspicious of malignancy or the serum PSA was > or = 4.0 ng/mL. An American Urological Association Symptom Index (AUA-SI) was obtained, and urine analysed using dipsticks. RESULTS: From May 2000 to November 2001, 660 men were assessed (mean age 59.4 years, range 30-82); 60.6% were Black African, 37.3% mixed (Coloured), 1.8% White (Caucasian) and 0.2% Asian (Indian). The mean (range) AUA-SI was 5.98 (0-35) in the whole group; the DRE was recorded as clinically suspicious of malignancy in 3.2%. The mean PSA was 20.39 (0.04-10 000) ng/mL in the whole group, but when two outliers (1865 and 10 000 ng/mL) were disregarded, it was 2.4 ng/mL. In Black patients the mean PSA was 31.8 (0.04-10 000) ng/mL, and without the outliers, 2.1 ng/mL; in Coloured patients it was 2.94 (0.05-50) ng/mL. The PSA was > or = 4.0 ng/mL in 9.6% of the whole group, in 7.8% of Black and in 13% of Coloured patients. Prostate biopsies were taken in 21 patients (3.2% of the whole group and a third of those with a PSA of > or = 4.0 ng/mL); in Black patients, biopsies were taken in 1.5% and 19.4%, respectively, and in Coloured patients in 6.1% and 46.9%, respectively. The prostate biopsy showed cancer in 43% of the whole group, in a third of Black and in 47% of Coloured patients; prostate cancer was detected in 1.4%, 0.5% and 2.8%, respectively. CONCLUSIONS: That prostate biopsies were obtained in only 19% of Black and in only 47% of Coloured men with a serum PSA of > or = 4.0 ng/mL is of concern. This indicates that there is a significant problem in getting men with an elevated serum PSA level to undergo a prostate biopsy in the primary healthcare setting in South Africa.

Adult↗
PubMed2002

Nomograms and instruments for the initial prostate evaluation: the ability to estimate the likelihood of identifying prostate cancer.

As a result of prostate cancer screening programs, approximately 10% of otherwise healthy men will be found to have an elevated prostate-specific antigen (PSA) level and therefore be at risk for harboring prostate cancer. Patients with an elevated PSA level have a wide variation in the risk for having prostate cancer diagnosed by transrectal ultrasound (TRUS)-guided prostate biopsy. To adequately counsel these patients, some form of individualized risk assessment must be given. There are several tables, artificial neural network (ANN) models, and nomograms that are available to stratify an individual patients risk for having prostate cancer diagnosed by a TRUS biopsy, either initially or on subsequent biopsies after a previous negative biopsy. Presently, nomograms are also being developed to predict the risk not only for having prostate cancer but also for clinically significant prostate cancer. The difficulty in calculating this risk for an individual patient is that the multiple competing clinical and pathologic factors have varying degrees of effect on the overall risk. This problem of competing risk factors can be overcome by the use of nomograms or ANNs. This article reviews the available instruments that are available to the urologist to enable prediction of the risk for having prostate cancer diagnosed by TRUS-guided prostate biopsy.

Biopsy↗