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Abstract
In the opinion of many urologists, prostate- specific antigen (PSA), which is not specific of any disease, is not considered in the diagnosis and follow-up of benign prostatic hyperplasia (BPH). Nonetheless, prostate cancer diagnosis is based on PSA screening. PSA value is thus available for a majority of men above 50. Recent data suggest that there is a link between PSA value and BPH natural history, turning PSA into a tool for BPH management and prevention of complications such as retention. It hasn't got into practice so far, as recommended criteria for PSA screening in BPH have not been issued. The debate over this topic is only at its beginning.
As the research of metabolic imaging is expanding, the clinical applications of radiolabeled substrates have also been increasing. Apart from glycolysis, other biochemical processes including amino acid synthesis, peptide and nucleic acid sequencing, lipid metabolism, signal transduction, and neurotransmitter-receptor interactions are also known to represent various forms of metabolic changes possibly found in tumor cells. In the literature, there are increasing amount of research studies on non-18F-FDG PET radiopharmaceuticals targeted for specific biochemical processes other than glycolysis. This chapter discusses on the basic biochemistry of non-18F-FDG PET tracers and how a good understanding of the underlying metabolic pathways of individual tracers leads to various clinical applications, particularly in the improvement of tumor detection, diagnosis, and patient management. Specific discussion is focused on 11C-acetate, 18F-acetate, 11C-choline, 18F-choline, 11C-methionine, 18F-DOPA, 18F-FLT, and Gallium-68 (68Ga)-labeled somatostatin analogs, primarily because these PET tracers have been investigated in greater biochemical and pharmaceutical details. Some have already been clinically confirmed useful, while others have great potentials to add to our understanding and to guide our research development on tumor metabolism and growth.
Objective
To analyze the incidence and main causes of mortality in the Department of Urology of the University Hospital of Cocody.
Patients and Methods
This retrospective analysis included 117 patients who died in the Department of Urology of the University Hospital of Cocody between April 2000 and December. Based on the data collected from the patient files, the hospital registry and the death certificates we studied the frequency and causes of death.
Results
The overall mortality rate was 10.1% with a male-to-female sex ratio of 14:1. The patients’ mean age was 63.4 (range 18–94) years. The main cause of death was cancer (87.5%). Cancer of the prostate which was the second most frequent reason for consultation after benign prostatic hyperplasia was the commonest cause of death encountered in 62.4% of the patients, followed by bladder and renal cancer with 16,2% and 6%, respectively. Prostatic adenoma (52%) was the most frequent and urethral stricture (8%) the third most frequent reason for hospitalization and led to death in 3.4% and 4.3%, respectively. Moreover, death mainly occurred in the second half of the month (53.9%) and during the night (57.3%).
Conclusion
The incidence of mortality in urology remains high and is almost exclusively related to urological cancers.
The ability of 11C-choline and multimodality fusion imaging with integrated PET and contrast-enhanced CT (PET/CT) was investigated to delineate prostate carcinoma (PCa) within the prostate and to differentiate cancer tissue from normal prostate, benign prostate hyperplasia, and focal chronic prostatitis.
All patients with PCa gave written informed consent. Twenty-six patients with clinical stage T1, T2, or T3 and biopsy-proven PCa underwent 11C-choline PET/CT after intravenous injection of 1,112 +/- 131 MBq 11C-choline, radical retropubic prostatovesiculectomy, and standardized prostate tissue sampling. Maximal standardized uptake values (SUVs) of 11C-choline within 36 segments of the prostate were determined. PET/CT results were correlated with histopathologic results, prostate-specific antigen (PSA), Gleason score, and pT stage.
The SUV of 11C-choline in PCa tissue was 3.5 +/- 1.3 (mean +/- SD) and significantly higher than that in prostate tissue with benign histopathologic lesions (2.0 +/- 0.6; P < 0.001 benign histopathology vs. cancer). Visual and quantitative analyses of segmental 11C-choline uptake of each patient unambiguously located PCa in 26 of 26 patients and 25 of 26 patients, respectively. A threshold SUV of 2.65 yielded an area under the receiver-operating-characteristic (ROC) curve of 0.89 +/- 0.01 for correctly locating PCa. The maximal 11C-choline SUV did not correlate significantly with PSA or Gleason score but did correlate with T stage (P = 0.01; Spearman r = 0.49).
11C-Choline PET/CT can accurately detect and locate major areas with PCa and differentiate segments with PCa from those with benign hyperplasia, chronic prostatitis, or normal prostate tissue. The maximal tumoral 11C-choline uptake is related to pT stage.
To evaluate longitudinal changes in prostate-specific antigen (PSA) levels in men with and without prostate disease.
Case-control study of men with and without prostate disease who were participants in a prospective aging study.
Gerontology Research Center of the National Institute on Aging; the Baltimore (Md) Longitudinal Study of Aging.
Sixteen men with no prostate disease (control group), 20 men with a histologic diagnosis of benign prostatic hyperplasia (BPH), and 18 men with a histologic diagnosis of prostate cancer.
Multiple PSA and androgen determinations on serum samples obtained from 7 to 25 years prior to histologic diagnosis or exclusion of prostate disease.
Changes in androgen levels with age did not differ between groups. Control subjects did not show a significant change in PSA levels with age. There was a significant difference in the age-adjusted rate of change in PSA levels between groups (prostate cancer greater than BPH greater than control; P less than .01). At 5 years before diagnosis when PSA levels did not differ between subjects with BPH and prostate cancer, rate of change in PSA levels (0.75 micrograms/L per year) was significantly greater in subjects with prostate cancer compared with control subjects and subjects with BPH. Also, rate of change in PSA levels distinguished subjects with prostate cancer from subjects with BPH and control subjects with a specificity of 90% and 100%, respectively.
The most significant factor affecting serum PSA levels with age is the development of prostate disease. Rate of change in PSA levels may be a sensitive and specific early clinical marker for the development of prostate cancer.
Purpose: Prostate specific antigen (PSA) is a predictor of prostate growth in men with lower urinary tract symptoms. The long-term risk of prostate enlargement as a function of PSA among community dwelling volunteers is unknown. Materials and Methods: A Cox proportional hazards regression model was used to study the relationship between baseline PSA level at ages 40 to 49.9 years in 194 men, 50 to 59.9 in 191 and 60 to 69.9 in 144, and prostate enlargement, defined as a prostate volume larger than the 75th percentile for age decade, as measured by magnetic resonance imaging in a longitudinal study of aging (Baltimore Longitudinal Study of Aging, National Institute on Aging). Kaplan-Meier survival analysis was performed to estimate the probability of freedom from prostate enlargement with time as a function of baseline PSA level. Results: The relative risk of prostate enlargement was 3- to 6-fold higher for men 40 to 49.9 years old with a baseline PSA of 0.31 ng./ml. or more compared to men with PSA levels of 0.30 ng./ml. or less at baseline. The relative risk was increased 5- to 9-fold in men 50 to 59.9 years old and 11-fold in those 60 to 69.9 years old when comparing men with PSA greater than 0.80 ng./ml. and greater than 1.70 ng./ml. with those with PSA 0.50 or less. The cumulative probability of freedom from prostate enlargement at 20 years was 0.89 (95% confidence interval ([CI] 0.79-0.99) and 0.63 (0.52-0.74) for men 40 to 49.9 years old with PSA levels below and above 0.30 ng./ml., respectively. For men 50 to 59.9 years old the 10-year probability of freedom from prostate enlargement was 0.90 (95% CI 0.84-0.96) and 0.59 (0.43-0.74) when PSA levels were below and above 0.80 ng./ml., respectively. At age 60 to 69.9 years the 10-year probability of freedom from prostate enlargement was 0.83 (95% CI 0.72-0.93) and 0.27 (0.09 to 0.48) when PSA levels were below and above 1.70 ng./ml., respectively. Conclusions: These data demonstrate the long-term risk of prostate enlargement by PSA level. Risk stratification based on PSA level may be useful to identify men at greatest risk for adverse events due to prostate enlargement and selection of men for future benign prostatic hyperplasia studies.
Objective.
——To evaluate longitudinal changes in prostate-specific antigen (PSA) levels in men with and without prostate disease.Design.
—Case-control study of men with and without prostate disease who were participants in a prospective aging study.Setting.
—Gerontology Research Center of the National Institute on Aging; the Baltimore (Md) Longitudinal Study of Aging.Patients.
—Sixteen men with no prostate disease (control group), 20 men with a histologic diagnosis of benign prostatic hyperplasia (BPH), and 18 men with a histologic diagnosis of prostate cancer.Outcome Measures.
—Multiple PSA and androgen determinations on serum samples obtained from 7 to 25 years prior to histologic diagnosis or exclusion of prostate disease.Results.
—Changes in androgen levels with age did not differ between groups. Control subjects did not show a significant change in PSA levels with age. There was a significant difference in the age-adjusted rate of change in PSA levels between groups (prostate cancer>BPH>control; P<.01). At 5 years before diagnosis when PSA levels did not differ between subjects with BPH and prostate cancer, rate of change in PSA levels (0.75 μg/L per year) was significantly greater in subjects with prostate cancer compared with control subjects and subjects with BPH. Also, rate of change in PSA levels distinguished subjects with prostate cancer from subjects with BPH and control subjects with a specificity of 90% and 100%, respectively.Conclusions.
—The most significant factor affecting serum PSA levels with age is the development of prostate disease. Rate of change in PSA levels may be a sensitive and specific early clinical marker for the development of prostate cancer.(JAMA. 1992;267:2215-2220)
Spontanous pratice of
screening in the population led to
diagnosis of prostate cancer at earlier
age and stage. Wide use of PSA
test impact on mortality decrease is
still difficult to analyse. However
authors agree that the initial reduction
of mortality is due to improved
treatment for advanced and metastatic
stages. More recent decrease
is due to PSA screening and
treatment of high grade and fast
growing localised stages. There is
the shift of incidence in favor of
localised stages which represented
80% of new cases in 2003 and allow
in these cases a curative management
by surgery or radiotherapy
alone. Desease prevalence, at stage
of recurence after a curative treatment
or advanced or metastatic
stage (20% of new cases) increases.
These stages are managed by
medical antitumoral treatment
alone or combined to a local treatment.
Prostate cancer management
today needs to be multidisciplinary,
including urologists, oncologists,
radiotherapists.
To define the characteristics of serum prostate-specific antigen (PSA) in a population of healthy men without clinically evident prostate cancer, but who are at risk for developing the malignancy. The influence of patient age and prostatic size on the serum PSA concentration was assessed in order to use PSA more appropriately to detect clinically significant prostate cancer at an early, potentially curable stage.
Prospective, community-based study.
Between December 1989 and March 1991, 2119 healthy men aged 40 to 79 years from Olmsted County, Minnesota, were entered into a prospective study to assess the natural history of benign prostatic hyperplasia. Of these, 537 (25%) were randomly chosen to participate in a detailed clinical examination that included a serum PSA determination (Tandem-R PSA assay), digital rectal examination, and transrectal ultrasonography. Four hundred seventy-one (88%) completed the prostatic evaluation and had no evidence of prostate cancer by any of these three diagnostic tests; these men formed the study population on which all analyses were performed.
Serum PSA concentration, prostatic volume, and PSA density (serum PSA level/prostatic volume) as a function of patient age.
The serum PSA concentration is correlated with patient age (r = .43; P < .0001) and prostatic volume (r = .55; P < .0001). Prostatic volume, in turn, is directly correlated with patient age (r = .43; P < .0001), whereas the PSA density value is only weakly correlated with patient age (r = .25; P < .001). For a healthy 60-year-old man with no evidence of prostate cancer, the serum PSA concentration increases by approximately 3.2% per year (0.04 ng/mL per year). The recommended reference range for serum PSA (95th percentile) for men aged 40 to 49 years is 0.0 to 2.5 ng/mL; for 50 to 59 years, 0.0 to 3.5 ng/mL; 60 to 69 years, 0.0 to 4.5 ng/mL; and 70 to 79 years, 0.0 to 6.5 ng/mL.
The serum PSA concentration is directly correlated with patient age and prostatic volume, the latter of which also is directly related to age. Thus, rather than rely on a single reference range for men of all age groups, it is more appropriate to have age-specific reference ranges. These age-specific reference ranges have the potential to make serum PSA a more discriminating tumor marker for detecting clinically significant cancers in older men (increasing specificity) and to find more potentially curable cancers in younger men (increasing sensitivity).
Prostate specific antigen (PSA) is a predictor of prostate growth in men with lower urinary tract symptoms. The long-term risk of prostate enlargement as a function of PSA among community dwelling volunteers is unknown.
A Cox proportional hazards regression model was used to study the relationship between baseline PSA level at ages 40 to 49.9 years in 194 men, 50 to 59.9 in 191 and 60 to 69.9 in 144, and prostate enlargement, defined as a prostate volume larger than the 75th percentile for age decade, as measured by magnetic resonance imaging in a longitudinal study of aging (Baltimore Longitudinal Study of Aging, National Institute on Aging). Kaplan-Meier survival analysis was performed to estimate the probability of freedom from prostate enlargement with time as a function of baseline PSA level.
The relative risk of prostate enlargement was 3- to 6-fold higher for men 40 to 49.9 years old with a baseline PSA of 0.31 ng./ml. or more compared to men with PSA levels of 0.30 ng./ml. or less at baseline. The relative risk was increased 5- to 9-fold in men 50 to 59.9 years old and 11-fold in those 60 to 69.9 years old when comparing men with PSA greater than 0.80 ng./ml. and greater than 1.70 ng./ml. with those with PSA 0.50 or less. The cumulative probability of freedom from prostate enlargement at 20 years was 0.89 (95% confidence interval ([CI] 0.79-0.99) and 0.63 (0.52-0.74) for men 40 to 49.9 years old with PSA levels below and above 0.30 ng./ml., respectively. For men 50 to 59.9 years old the 10-year probability of freedom from prostate enlargement was 0.90 (95% CI 0.84-0.96) and 0.59 (0.43-0.74) when PSA levels were below and above 0.80 ng./ml., respectively. At age 60 to 69.9 years the 10-year probability of freedom from prostate enlargement was 0.83 (95% CI 0.72-0.93) and 0.27 (0.09 to 0.48) when PSA levels were below and above 1.70 ng./ml., respectively.
These data demonstrate the long-term risk of prostate enlargement by PSA level. Risk stratification based on PSA level may be useful to identify men at greatest risk for adverse events due to prostate enlargement and selection of men for future benign prostatic hyperplasia studies.
To assess the utility of voiding and filling symptom subscores in predicting features of benign prostatic hyperplasia (BPH) progression, including acute urinary retention (AUR) and prostate surgery.
The Proscar Long-term Efficacy and Safety Study (PLESS) was a 4-year study designed to evaluate the effects of finasteride versus placebo in men with lower urinary tract symptoms (LUTS), clinical evidence of BPH, and no evidence of prostate cancer. A self-administered questionnaire was employed to quantify LUTS at baseline. Receiver operating characteristics (ROC) curves were used to assess baseline characteristics from patients treated with placebo as predictors of outcomes. The characteristics assessed included the overall symptom score (Quasi-AUA SI), separate voiding and filling subscores, prostate volume (PV) and serum prostate-specific antigen (PSA) levels.
PV and PSA were superior to the symptom scores at predicting episodes of spontaneous AUR and all types of AUR. The Quasi-AUA SI and the filling and voiding subscores were effective at predicting progression to surgery; however, PSA was more effective at predicting this outcome. To better evaluate symptoms as predictors of surgery, patients who experienced a preceding episode of AUR were excluded from the surgery analysis. In the absence of preceding AUR, the best predictors of future surgery were the Quasi-AUA SI and the filling subscore.
Among men with LUTS, clinical BPH and no history of AUR, the overall symptom score and storage subscore are useful parameters to aid clinicians in identifying patients at risk for future prostate surgery. PV and PSA were the best predictors of AUR, while PSA was the best predictor of prostate surgery (for all indications).
Free prostate specific antigen (PSA) in serum consists of heterogeneous molecular subforms. Recently we developed an immunoassay for selective measurement of a subfraction of free PSA called intact PSA, which has been shown to be closely associated with prostate cancer. We assessed the ability of serum intact PSA to discriminate between benign and malignant prostatic disease.
In serum of 178 men with benign disease and 255 men with prostate cancer we measured total PSA and free PSA using a commercially available immunoassay. Intact PSA levels were analyzed by a newly developed assay specific for noncleaved, that is single chain forms of free PSA. Internally cleaved "nicked" PSA was calculated by subtracting intact from free PSA. We also calculated ratios of intact PSA-to-free PSA (intact-to-free PSA) and nicked PSA-to-total PSA (nicked-to-total PSA). We compared means, medians and ranges of all analytes and ratios in patients with and without cancer for the entire total PSA range and in a subset with total PSA ranging from 2 to 10 ng./ml. Furthermore, various combinations of PSA forms were tested for their predictive ability. For statistical comparison we used the Mann-Whitney U test and ROC analysis.
The ratio intact-to-free PSA was significantly higher in cancer (median 48.5%) compared to noncancer cases (median 41.8%, p <0.0001). Conversely, the ratio nicked-to-total PSA was significantly higher in men without compared to those with prostate cancer (median 11.0% and 6.0%, respectively, p <0.0001). Highest discriminative ability was observed for a combination of intact, total and free PSA (log [intact, free, total], AUC = 0.773) followed by nicked-to-total PSA (AUC 0.755). In the subgroup of patients with total PSA levels from 2 to 10 ng./ml. only the AUC of log intact, free, total (AUC 0.706, p = 0.0017) and nicked-to-total PSA (AUC 0.704,p = 0.0019) were significantly larger compared to the AUC of total PSA (AUC 0.602).
By contrast to measuring crude free PSA concentration, selective determination of specific free PSA subforms, intact PSA and nicked PSA proved to be useful to discriminate men with benign from malignant prostatic disease. These markers may serve to generate specific serum profiles of PSA for improved specificity and early detection of prostate cancer. To translate the encouraging statistical advantage shown in this study into a clinically applicable tool warrants further investigation.
Physicians commonly screen for prostate cancer by using prostate-specific antigen (PSA) and digital rectal examination (DRE). The usefulness of these screening mechanisms is not well established, however. A meta-analysis of PSA and DRE to detect prostate carcinoma was conducted with a focus on sensitivity, specificity, and positive predictive value.
A literature search of OVID database (1966 to November 1999) using the medical subject headings "prostate-specific antigen" and "mass screening," as well as "prostate carcinoma," was performed. Thirteen articles were selected for the meta-analysis in this study. Most studies included asymptomatic men older than 50 years from various countries. Pooled results were calculated from the individual reports for sensitivity, specificity, and positive predictive value for PSA and DRE based on biopsy result as the reference standard.
The overall detection rate of prostate carcinoma was 1.8% based on a positive biopsy. Of the prostate carcinoma detected, 83.4% was localized. The pooled sensitivity, specificity, and positive predictive value for PSA were 72.1%, 93.2% and 25.1%, respectively; and for DRE were 53.2%, 83.6% and 17.8%, respectively.
There were two major outcomes of this meta-analysis. One was the potential for detecting early-stage prostate cancer with these screening tests, because 83.4% of total cancers detected were localized. The second important outcome was that the overall sensitivity, specificity, and positive predictive value for PSA were higher than those for DRE when used as a screening tool to detect prostate cancer. When a patient has abnormal findings using PSA and DRE, the chance of cancer is 1 in 4 or 5. Conversely, when findings from PSA and DRE are normal, the chance of missing a cancer is about 10%.
This study was designed to use a prospectively analyzed, population-based, multiethnic cohort of men to determine if there is a relationship between one measure of obesity/overweight (Body Mass Index) and Prostate Specific Antigen (PSA). A total of 1565 men without a prior diagnosis of prostate cancer were prospectively enrolled in the San Antonio study of Biomarkers Of Risk (SABOR) Clinical and Epidemiologic Center of the Early Detection Research Network of the National Cancer Institute. Body Mass Index (BMI) was compared with serum PSA levels, stratifying by ethnic group. No relationship was found between BMI and PSA in any ethnic group or in the cohort as a whole. This study suggests that there is no increased risk of overdetection of prostate cancer among obese men due to an elevation in PSA.
Proscar Long-term Efficacy and Safety Study. Storage (irritative) and voiding (obstructive) symptom as predictors of BPH progression and retated outcomes
- Roehrborn Cg Mcdonneu Jd
- B Sattzman
- D Bergner
- T Gray
- P Narayan
Roehrborn CG, McDonneU JD, Sattzman B, Bergner D, Gray T, Narayan P, et aL PLESS Study Group. Proscar Long-term Efficacy and Safety Study. Storage (irritative) and voiding (obstructive) symptom as predictors of BPH progression and retated outcomes. Eur UroÁ 2002;42:1-6.
AUA guideline on management of BPH Chapter l: diagnosis and treatment recommendations
- Guideunes Aua
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AUA Practice GuideUnes Committe, AUA guideline on management of BPH (2003). Chapter l: diagnosis and treatment recommendations, d Urol 2003; 170:530-47.
D&pistage du cancer de (a prostate
- X Souu~
ViUers A, Rebi[tard X, SouU~ M. D&pistage du cancer de (a prostate. Pro~ Urol 2003; 1:3:209-14.
Discrimination of benign from malignant prostatic disease by sélective measurements of sin gle chais, intact free prostate-specific antigen
- Steuber
Editorial comment to 9
- I M Thompson
- R Leach
Proscar Long-term Efficacy and Safety Study. Storage (irritative) and voiding (obstructive) symptom as predictors of BPH progression and related outcomes
- Roehrborn