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PubMed2005

Screening for prostate cancer.

Epidemiologically, prostate cancer is the most common cancer in the Western world after skin cancer. To date, it is still unknown whether screening for prostate cancer is justified, because results of randomised clinical trials are not yet available. The available screening tests (i.e. prostate-specific antigen (PSA) test) do not always detect cancers that otherwise would have resulted in prostate cancer mortality. Favourable results from prostate cancer screening include an increasing number of men with localised disease and an increase in the number of well-differentiated tumours. However, the risk of overdiagnosis and subsequent over-treatment (due to the diagnosis of localised disease), using aggressive therapies fuels arguments against screening. Therefore, until more evidence is available proving otherwise, prostate cancer screening can only be justified in the context of clinical trials.

Biopsy↗

PubMed2001

Prostate cancer: horizons in the development of novel anti-cancer strategies.

Prostate cancer is the most common cause of non-cutaneous cancer in men and a leading lethal malignancy with increasing incidence worldwide. Inevitably, all patients will develop androgen-independent disease, which remains the main obstacle to improving survival. Unfortunately, existing first and second line hormonal treatment are condemned to extent survival for only a few years. These sobering data have forced researchers to start exploring in depth the molecular mechanisms implicated in the emergence of androgen independence and of prostate cancer invasion. In this vein, epoch-making discoveries in molecular oncology along with rapid expansion of our knowledge concerning the processes that govern differentiation, apoptosis, immune surveillance, angiogenesis, metastasis, cell cycle and signal transduction control, have unveiled a plethora of specific targets for prostate cancer gene therapy, immunotherapy and anti-invasion therapy, along with a variety of small-molecule compounds which inhibit or stimulate these pathways. These new anti-cancer approaches are in various stages of clinical development, providing exciting perspectives for the future of prostate cancer cure and enriching the current anti-cancer drug quiver with a new spectrum of therapeutic agents. The present review, through extensive literature cross-examination, discusses several novel anti-prostate cancer strategies, emphasizing on approaches that potentially may extend end-stage patient's survival.

Angiogenesis Inhibitors↗

PubMed1993

American Cancer Society--National Prostate Cancer Detection Project. Results from multiple examinations using transrectal ultrasound, digital rectal examination, and prostate specific antigen.

BACKGROUND: The American Cancer Society-National Prostate Cancer Detection Project is a prospective study of the feasibility of early prostate cancer detection by digital rectal examination (DRE), transrectal ultrasound (TRUS), and prostate specific antigen (PSA). Two thousand nine hundred ninety-nine men not previously suspected of having prostate cancer have been entered on study in ten participating clinical centers. METHODS: The study protocol requires these men to undergo testing with the three detection methods under investigation on an annual basis for up to 5 years. Data currently are available on 1972 men who have completed protocol requirements for two sequential series of examinations. RESULTS: At the first visit, it was recommended that 16.5% of subjects undergo biopsy based on the TRUS and/or DRE findings. Seventy-three (3.7%) men were found to have cancer after the first series of examinations. When the 1899 men who did not have cancer were reexamined, in 11.4%, a biopsy was recommended, and an additional 33 (1.7%) cancers were detected. Cancer detection rates were higher in older men, and the sensitivity of TRUS was higher than that of DRE at both examinations. The positive predictive values (PPV) of TRUS and DRE varied significantly depending on the PSA level; PPV decreased at the second examination. Positive findings during the second examination were associated with elevated PSA levels during the earlier visit and rising PSA levels between examinations. Analyses of the 106 cancers detected currently showed a preponderance of early-stage cancer and low Gleason scores. CONCLUSIONS: It may be possible to increase the early detection of prostate cancer by periodic examination by a combination of detection modalities.

Aged↗

PubMed2002

Large-scale randomized prostate cancer screening trials: program performances in the European Randomized Screening for Prostate Cancer trial and the Prostate, Lung, Colorectal and Ovary cancer trial.

Two large-scale randomized screening trials, the Prostate, Lung, Colorectal and Ovary (PLCO) cancer trial in the USA and the European Randomized Screening for Prostate Cancer (ERSPC) trial in Europe are currently under way, aimed at assessing whether screening reduces prostate cancer mortality. Up to the end of 1998, 102,691 men have been randomized to the intervention arm and 115,322 to the control arm (which represents 83% of the target sample size) from 7 European countries and 10 screening centers in the USA. The principal screening method at all centers is determination of serum prostate-specific antigen (PSA). The PLCO trial and some European centers use also digital rectal examination (DRE) as an ancillary screening test. In the core age group (55-69 years), 3,362 of 32,486 men screened (10%) had a serum PSA concentration of 4 ng/ml or greater, which is 1 cut-off for biopsy (performed in 84%). An additional 6% was referred for further assessment based on other criteria, with much less efficiency. Differences in PSA by country are largely attributable to the age structure of the study population. The mean age-specific PSA levels are lower in the PLCO trial (1.64 ng/ml [in the age group 55-59 years], 1.80 [60-64 years] and 2.18 [65-69 years) than in the ERSPC trial (1.28-1.71 [55-59], 1.75-2.87 [60-64] and 2.48-3.06 [65-69 years]). Detection rates at the first screen in the ERSPC trial range from 11 to 42/1,000 men screened and reflect underlying differences in incidence rates and screening procedures. In centers with consent to randomization design, adherence in the screening arm is 91%, but less than half of the men in the target population are enrolled in the trial. In population-based centers in which men were randomized prior to consent, all eligible subjects are enrolled, but only about two-thirds of the men in the intervention arm undergo screening. Considerable progress has been made in both trials. Enrollment will be completed in 2001. A substantial number of early prostate cancers have been detected. The differences between countries seem to reflect both underlying prostate cancer incidence and screening policy. The trials have the power to show definitive results in 2005-2008.

Aged↗

PubMedDate not supplied

The MXI1 tumor suppressor gene is not mutated in primary prostate cancer.

For prostate cancer, allelic deletions from the long arm of chromosome 10 (#10q23-25), the locus of the putative tumor suppressor gene MXI1 (#10q24-25), have been identified as a frequently occurring genetic event. During the development of several human malignancies, the c-myc proto-oncogene has been identified to enhance cellular transformation, mitogenesis and cell proliferation. The MXI1 gene, belonging to the helix-loop-helix (bHLH) gene family, was demonstrated to display tumor suppressor function by antagonizing c-myc induced transcriptional activities. Due to the detection of point mutations in the retained alleles of four primary adenocarcinomas of the prostate, MXI1 gene alterations have been suggested to be involved in the development and/or the progression of prostate cancer. To evaluate the role of MXI1 gene alterations for the development of adenocarcinoma of the prostate, 42 primary prostate cancers of different stage (T1-4) and histological grade (G1-3) were investigated for alterations within exons 4 and 5 of the MXI1 gene (spanning 6 exons in total), encoding for the functional HLH-Zip domain, by RNA-SSCP analysis and direct PCR-DNA-sequencing following the microscopically guided tumor cell dissection from 5 microm fresh-frozen buffer-soaked tissue sections. Even by application of this highly elaborated technical approach, MXI1 gene alterations could not be deleted in any of the tumor specimens investigated. Therefore, a substantial involvement of MXI1 gene alterations in the development of prostate cancer appears unlikely. The newly identified putative tumor suppressor gene PTEN, located at #10q23, might be responsible for the frequently observed allelic deletions from #10q23-25 in prostate cancer.

Adenocarcinoma↗

PubMed1999

Elevation of cyclic adenosine 3',5'-monophosphate potentiates activation of mitogen-activated protein kinase by growth factors in LNCaP prostate cancer cells.

Prostate cells are simultaneously exposed to a variety of peptide growth factors and neuropeptides that elevate cAMP. Both the growth factors and cAMP have large effects on the growth, differentiation, and movement of many cell types. Because mitogen-activated protein kinase (MAPK) is central to these effects, we analyzed the ways in which these agonists interact in regulating MAPK in prostate cancer cells. We show that, in LNCaP prostate cancer cells, elevation of intracellular cAMP can potentiate the ability of epidermal growth factor (EGF), interleukin 6, and serum to activate MAPK and that this potentiation depends on protein kinase A and Rap1. The response to cAMP is different in the androgen-independent prostate cancer cell line PC-3, where elevation of cAMP slightly inhibits MAPK activation by EGF. We also show that treatment of LNCaP with the calcium ionophore A23187 or the phorbol ester phorbol 12-myristate 13-acetate activates MAPK, but the activation of MAPK by these agonists is inhibited rather than potentiated by increasing cAMP. Finally, we show that phorbol 12-myristate 13-acetate and interleukin 6 can potentiate the signaling activity of EGF. We conclude that neuroendocrine factors that elevate cAMP sensitize LNCaP prostate cancer cells to signaling by peptide growth factors and that low levels of mixtures of growth factors can activate intracellular signaling to a greater degree than would be predicted from the activity of the individual agonists.

Blood Proteins↗

PubMed1983

Radioimmunodetection of prostatic cancer. In vivo use of radioactive antibodies against prostatic acid phosphatase for diagnosis and detection of prostatic cancer by nuclear imaging.

Radioimmunodetection (RAID) of prostatic cancer is done by injecting 131I-labeled rabbit antibody IgG against prostatic acid phosphatase (PAP) and performing total-body photoscans with a gamma scintillation camera. Of two patients tested, the PAP RAID scintiscans located the primary or recurrent prostatic cancers in both and showed no disease in the lungs of the patient shown subsequently to have lung cancer. The lung tumor nodules showing anti-PAP IgG accretion were assumed to be of prostatic cancer origin, since one of the original tumors removed from this patient's other lung a year earlier stained for PAP by immunohistochemistry. This study showed that PAP RAID can locate primary and metastatic tumors of prostatic origin.

Acid Phosphatase↗

PubMed1997

Prostate-specific antigen and early detection of prostate cancer.

Prostate-specific antigen (PSA) is biochemically a 33-kDa serine protease and is the prototype of tumor marker most useful in investigating basic science and clinical application of prostate cancer. As an immunohistopathological marker, PSA is especially effective in the identification of distant metastatic prostate carcinoma and in the differential diagnosis of poorly differentiated transitional cell carcinomas of the bladder from prostate carcinoma. As a serologic marker, PSA is most useful in staging, monitoring and in early detection of recurrent disease. The greatest value of PSA is as a screening aid along with digital rectal examination for early detection of prostate cancer. PSA-based screening tests have been performed in various regions of the world and have yielded prostate cancer detection rates proportional to that of incidence rates in the countries. Most significantly, PSA detects early nonpalpable prostate cancer. Approximately 85% of the prostate tumors detected through PSA have the clinical features associated with medically important cancer. Further, a majority of the tumors, 70%, are confined to the organ. Although the issues of cost-benefit and increase in ultimate survival rate are still being evaluated in two large-scale randomized national trials, timely and definitive therapies of these potentially lethal tumors can result in high cure rate and improve the quality of patients' life.

Biomarkers, Tumor↗

PubMed2004

Serum proteomic profiling can discriminate prostate cancer from benign prostates in men with total prostate specific antigen levels between 2.5 and 15.0 ng/ml.

PURPOSE: Artificial intelligence based pattern recognition algorithms have been developed and successfully used to analyze complex serum proteomic data streams generated by surface enhanced, laser desorption ionization time-of-flight mass spectroscopy. In the current study we used a high performance, hybrid quadrupole time-of-flight mass spectrometer to generate discriminatory serum proteomic profiles to determine if this technology could be used to determine the need for prostate biopsy in men with elevated prostate specific antigen (PSA). MATERIALS AND METHODS: Serum samples were collected from 154 men with serum PSA 2.5 to 15.0 ng/ml and/or abnormal digital rectal examination prior to transrectal ultrasound guided biopsy. Serum samples were applied to WCX2 (weak cation exchange protein chip) Protein Arrays (Ciphergen Biosystems, Fremont, California) by a Biomek 2000 robotic liquid handler (Beckman-Coulter, Chaska, Minnesota) and low molecular weight (less than 20 kDa) proteomic patterns were generated with an API QSTAR Pulsar i LC/MS/MS System (Applied Biosystems, Framingham, Massachusetts). High resolution mass spectra were analyzed with a pattern recognition bioinformatics tool, that is Proteome Quest beta version 1.0 (Correlogic Systems, Inc., Bethesda, Maryland), in an attempt to identify and discover key discriminating ion signatures. Serum samples from 63 men (2 or more negative prostate biopsies in 23, 1 negative biopsy in 10 and biopsy detected prostate cancer [CaP] in 30) were used to train the diagnostic algorithm. The remaining 91 samples, including 28 of prostate cancer and 63 of 1 or more negative biopsies, were analyzed in blinded fashion. RESULTS: The most discriminatory model was found using the WCX2 chip. Testing the remaining 91 men with this model yielded 100% sensitivity and 67% specificity. In other words, if the proteomic pattern had been used to determine the need for prostate biopsy in this cohort of men with PSA between 2.5 and 15.0 ng/ml, 67% (42 of 63) with negative biopsies would have avoided unnecessary biopsy, while no cancers would have been missed. CONCLUSIONS: Our data demonstrate that high resolution mass spectroscopy can generate serum proteomic patterns that discriminate men with elevated PSA due to benign processes from men with CaP even when PSA is within the diagnostic gray zone. We are currently expanding the testing set to determine the reliability of this new technology to decrease unnecessary prostate biopsies without compromising the detection of curable CaP.

Algorithms↗

PubMed1993

[Side effects of estrogen administration to prostatic cancer patients: clinical and statistical survey of 109 prostatic cancer cases of Kyoto University Hospital].

Since the introduction of hormonal treatment for prostatic cancer by Huggins and Hodges in 1941, severe side effects of synthetic estrogen, which have overcome its benefit, have been reported in the U.S.A. and in European countries. However, in Japan the adverse effects of estrogen have been reported to be milder than in western countries, and estrogen still has an important role in the treatment of prostatic cancer in Japan. In this communication, the side-effects of synthetic estrogen administered to 109 prostatic cancer patients, who were admitted to Kyoto University Hospital between 1980-1990 are reported. Fifty-three (48.6%) of the 109 patients suffered adverse side effects of the estrogen, specifically cardiac disease (20.2%), fluid retention (14.7%) and hypertension (13.8%). Five of these patients died. Among the risk factors analyzed, daily dose, past history of cardio-vascular disease and ECG abnormalities were significantly correlated with the appearance of adverse effects. The reasons why the frequency of lethal side-effects is lower in our cases compared to findings reported by the Veterans Administration group may be the lower daily dose and cessation of estrogen administration when mild adverse effects appear and some other unknown factors, although the background of the patients and method of analysis are not comparable among them. The overall frequency of side-effects in prostatic cancer patients administered estrogen in our cases is not necessarily lower than in western countries, but the severity of the side effects was milder in our cases. We must be a ware of the potential adverse effects of estrogen.

Adult↗

PubMed1997

Relationship between prostate-specific antigen, clinical stage, and degree of bone metastasis in patients with prostate cancer: comparison with prostatic acid phosphatase and alkaline phosphatase.

BACKGROUND: The study was designed to examine the relation of the levels of prostate-specific antigen (PSA), prostatic acid phosphatase (PAP), and alkaline phosphatase (ALP) to clinical stage and bone metastasis in prostate cancer patients. METHODS: Serum PSA, PAP, and ALP levels were evaluated in 272 patients with prostate cancer. The relation of the level of PSA, PAP, and ALP to clinical stage and to degree of bone metastasis were examined by a multiple comparison method using ranks. The superiority of a marker in the rate of detection of bone metastasis was evaluated with receiver operating characteristic (ROC) curves. The correlation coefficients of the order of the extent of bone metastasis with PSA, PAP, and ALP were examined with Spearman's rank order correlation coefficient test. RESULTS: The levels of PSA showed significant differences among 8 pairs of clinical stages. In contrast, the levels of PAP showed significant differences among 6 pairs, and the levels of ALP showed significant differences among only 4 pairs. The area under the ROC curves of PSA, PAP, and ALP for revealing bone metastasis was 84.9%, 81.4%, and 77.3%, respectively. The correlation coefficients of the order of extent of disease (EOD) with log (PSA), log (PAP), and log (ALP) were 0.346, 0.394, and 0.618, respectively, and the levels of ALP showed the most significant differences regarding the extent of bone metastasis. CONCLUSION: PSA was the best marker for differentiating clinical stages, but showed limited reliability for stratifying the extent of bone metastasis.

Acid Phosphatase↗

PubMed1990

Serum of patients with prostatic cancer or benign prostatic hypertrophy contains nonpolar testosterone.

We have previously described a nonpolar form of radioimmunoassayable serum testosterone (NPT) not measured by available antitestosterone antibodies. It is detected by mild alkaline hydrolysis of the petroleum ether extract of serum and subsequent radioimmunoassay. The properties of NPT are consistent with that of a fatty acid ester of testosterone or dihydrotestosterone. The serum of young males contains 1 to 3 ng/ml NPT, but it is not detected in female serum. We measured serum testosterone and NPT levels in 36 men between 58 and 87 years of age. Seventeen subjects with advanced prostatic cancer (NPT 1.70 +/- 1.44 ng/ml) were compared with a control group consisting of six patients with benign prostatic hypertrophy (BPH) and 13 patients with no prostatic disease (NPT 0.72 +/- 0.46, P = 0.017). There was no significant difference between BPH patients and patients with no prostatic disease; the results were pooled. The concentration of NPT in prostatic cancer patients but not in controls was inversely correlated with that of testosterone. Immunoassayable testosterone was present in the serum of two orchiectomized patients and, therefore, cannot derive solely from the testes.

Aged↗

PubMed1999

Screening for prostate cancer with the prostate-specific antigen test: are patients making informed decisions?

BACKGROUND: The benefits of early detection of prostate cancer are uncertain, and the American College of Physicians and the American Academy of Family Physicians recommend individual decision making in prostate cancer screening. This study reports the knowledge of male primary care patients about prostate cancer and prostate-specific antigen (PSA) testing and examines how that knowledge is related to PSA testing, preferences for testing in the future, and desire for involvement in physician-patient decision making. METHODS: The sample included 160 men aged 45 to 70 years with no history of prostate cancer who presented for care at a university-based family medicine clinic. Before scheduled office visits, patients completed a questionnaire developed for this study that included a 10-question measure of prostate cancer knowledge, the Deber-Kraestchmer Problem-Solving Decision-Making Scale, sociodemographic indicators, and questions on PSA testing. RESULTS: In general, patients who were college graduates were more knowledgeable about prostate cancer and early detection than those with a high school education or less. Aside from college graduates, most patients could not identify the principle advantages and disadvantages of PSA testing. Patients indicating previous or future plans for PSA testing demonstrated greater knowledge than other patients. Desire for involvement in decision making varied by patient education but was not related to past PSA testing. CONCLUSIONS: Patients lack knowledge about prostate cancer and early detection. This knowledge deficit may impede the early detection of prostate cancer and is a barrier to making an informed decision about undergoing PSA testing.

Adult↗

PubMed2002

Prostate cancer screening with prostate specific antigen in spinal cord injured men.

PURPOSE: As the spinal cord injured population ages, prostate cancer becomes a more significant cause of potential mortality. Consequently due to various bladder management techniques the validity of standard prostate specific antigen (PSA) screening values in this population must be evaluated. We compared screening PSA values in a large population of spinal cord injured patients with those in age matched, nonspinal cord injured men. MATERIALS AND METHODS: Screening PSA values were obtained using the AxSYM assay (Abbott Laboratories, Abbott Park, Illinois) in 366 spinal cord injured men 40 to 79 years old. In those with PSA elevated to greater than 4 ng./ml. who consented to further evaluation standard sextant needle biopsy of the prostate were performed under transrectal ultrasound guidance. Data were compared with data on 371 randomly selected, age matched controls from the Baylor College of Medicine community screening program database of more than 19,000 patient-tests. Analysis was performed with the unpaired Student t test. RESULTS: When we divided patients 40 to 80 years old into 4 age groups by decade and compared them with normal controls by decade, there was no statistically significant difference in mean PSA in the 2 groups. Of 18 spinal cord injured patients with PSA greater than 4 ng./ml. 12 underwent transrectal ultrasound guided needle biopsy of the prostate and 6 refused further evaluation. Five of these biopsies (1.3% overall) were positive and 7 were negative for adenocarcinoma. CONCLUSIONS: As in healthy men, PSA and digital rectal examination can be performed in spinal cord injured men to screen for prostate cancer. None of the various bladder management techniques in these cases seemed to affect screening results.

Adenocarcinoma↗

PubMed2005

[Innovative concepts in early cancer detection and staging of localized prostate cancer].

Prostate cancer is the most common malignancy in males. Men aged 50 years and older are recommended to undergo an annual digital rectal examination (DRE) and determination of prostate-specific antigen (PSA) in serum for early detection. Fortunately, disease-specific mortality continues to decline as a result of advances in screening, staging, and patient awareness. However, about 30% of men with a clinically organ-confined disease show evidence of extracapsular extension or seminal vesicle invasion on pathological analysis. Consequently, there is a need for more accurate diagnostic tools for planning tailored treatment. A variety of modern imaging techniques has been implemented in an attempt to obtain more precise staging, thereby allowing for more detailed counseling, and instituting optimum therapy. This review highlights developments in prostate cancer imaging that may improve staging and treatment planning for prostate cancer patients.

Biomarkers, Tumor↗

PubMed1991

Peripheral hormone levels in controls and patients with prostatic cancer or benign prostatic hyperplasia: results from the Dutch-Japanese case-control study.

The possible relationship between changes in peripheral hormone levels and the occurrence of prostatic pathology was studied in a case-control study, involving estimation of various plasma hormones in 368 Dutch and 258 Japanese men, who were grouped as controls and patients with benign prostatic hyperplasia, focal prostatic carcinoma, or clinically evident prostatic carcinoma. Results of a number of previous, smaller studies concerning interrelationships between hormone levels in elderly men were confirmed within the Dutch and Japanese groups. Plasma levels of testosterone and estradiol were significantly lower in the Japanese men, when compared with those in Dutch men. Probably as a result of this difference in testosterone levels, the ratio between serum levels of testosterone and sex hormone-binding globulin (SHBG) was decreased in the Japanese men, while the ratio between the concentrations of dihydrotestosterone and testosterone was increased. These differences were also found when results from Japanese subgroups (controls and patients with prostate pathology) were compared with those from the Dutch subgroups. There were no significant differences in plasma androgen levels between Japanese or Dutch prostate cancer cases and their respective control subgroups. These findings do not support a correlation between the lower plasma testosterone levels and a lower incidence of prostate cancer in the Japanese men. Furthermore, no significant differences were found between salivary levels of testosterone or the ratio between testosterone and SHBG in the various Dutch subgroups. In Japanese benign prostatic hyperplasia patients, the testosterone to SHBG ratio was significantly increased. In conclusion, the results of this retrospective, cross-sectional study do not indicate that hormonal levels play a primary role in the origin or promotion of prostatic abnormalities. The finding of a lower plasma testosterone in the Japanese men, however, remains suggestive, warranting a more extensive prospective study.

Age Factors↗

PubMed1987

Pattern of care and follow-up of stages A1, B1 prostatic cancers from multicenter group, the National Prostatic Cancer Treatment Group (NPCTG).

In 1981, the National Prostatic Cancer Treatment Group began an open survey of available A1, B1 prostatic adenocarcinomas to determine outcome and clinical characteristics. Their report as of September, 1985, summarizes the outcome and important features of the survey. The majority of A1 cases had a low tumor grade I and were followed. Stage B1 received surgery or radiation generally. The B1 tumor grade was approximately one-third grade I, II, or III-IV. Presently, symptoms differ, as would be expected. Follow-up data to date have indicated no major changes. In some of the special study cases (12/52), the stage was changed as a result of the central laboratory review.

Adenocarcinoma↗

PubMed1979

The histochemical behaviour, electrophoretic mobility and distribution in cell fractions of acid phosphatase isozymes in prostatic cancer and benign prostate hyperplasia.

Acid phosphatase isozymes were investigated in cancerous prostatic tissue (4 cases) and benign prostatic hyperplasia (6 cases). Electron-microscopic histochemical examination of cancer tissue revealed irregular acid beta-glycerophosphatase staining in various cell organelles, including the plasma membrane, which was not seen in non-malignant tissue. Cancerous tissue homogenates also contained isozymic acid phosphatase species with high electrophoretic mobility, which was not detectable in benign tissue unless treated with detergent. Fractionation by differential centrifugation confirmed that much of the acid phosphatase activity in cancer tissue was extra-lysosomal. The detection of these isozyme properties may provide an opportunity, by means of tissue investigations, to define tumour stages earlier than on the basis of increased levels of serum acid phosphatase activity indicative of stage IV (D) prostatic cancer.

Acid Phosphatase↗