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PubMed2001

Prospective detection of clinically relevant prostate cancer in the prostate specific antigen range 1 to 3 ng./ml. combined with free-to-total ratio 20% or less: the Aarau experience.

PURPOSE: Little is known about the incidence rate and clinical relevance of prostate cancer in a low prostate specific antigen (PSA) level. In a prospective PSA based screening study we investigated the incidence and clinicopathological features of prostate cancer that occurred within PSA range 1 to 3 ng./ml. when the free-to-total ratio was 0.20 or less. MATERIALS AND METHODS: Men participating in the Aarau, Switzerland, section of the European Randomized Study of Screening for Prostate Cancer between October 1998 and July 2000 were included in the study. As a side study, all men with PSA between 1 and 3 ng./ml. and free-to-total ratio 0.20 or less were invited to undergo further evaluation with ultrasound guided sextant prostate biopsy. RESULTS: Overall, 168 (7.8%) participants fulfilled inclusion criteria. A total of 158 (94%) patients underwent prostate biopsy, and prostate cancer was detected in 17 (10.8%). There were no statistically significant differences between prostate cancer and benign prostatic hyperplasia in regard to patient age (60.7 versus 59.8 years), prostate volume (23.9 versus 23.0 cc), PSA (1.98 versus 1.86 ng./ml.), free-to-total ratio (0.161 versus 0.160), PSA density (0.089 versus 0.076 ng./ml.) or PSA transition zone density (0.33 versus 0.24 ng./ml., respectively). Median Gleason score was 5 on prostate biopsy versus 6 on retropubic prostatectomy specimen. Of the 14 patients who underwent surgery there were positive lymph nodes in 1, stage pT3b Gleason 7 disease in 1, and pathologically organ confined Gleason 5 in 2, Gleason 6 in 5 and Gleason 7 in 5. Mean tumor volume was 1.01 cc (range 0.02 to 5.17). There were 2 (14.3%) insignificant (less than 0.2 cc, Gleason grade 3 or less), 1 (7.1%) minimal (less than 0.5cc, Gleason grade 3 or less) and 11 (78.6%) clinically relevant and potentially harmful cancers. CONCLUSIONS: There is a significant number of prostate cancer cases diagnosed at PSA as low as 1 to 3 ng./ml. A majority of these tumors are clinically significant. This free-to-total ratio range may be helpful for identifying prostate cancer. The "window of opportunity" for detection of curable cancer may change in populations with higher life expectancy towards lower PSA. Lack of specificity and characterization of tumor aggressiveness remains an unsolved issue for PSA.

Aged↗

PubMed1994

[Management of advanced prostate cancer].

Prostatic adenocarcinoma is still often detected at an advanced stage, despite efforts for earlier diagnosis. Treatment depends especially on the stage of the disease at the time of diagnosis, on potential development which varies among types of tumours, on the presence of symptoms related to local-regional or general dissemination, and on age, which may be advanced in these patients. In stage C cancers with limited extraprostatic dissemination, the use of radical prostatectomy is debated. It may be indicated in some selected young patients in association with hormonal treatment. In other cases, androgen control alone (early, or only after appearance of symptoms) or pelvic radiation therapy can be used. In the presence of metastases, hormonal control is the best means of slowing disease progression. It is always indicated when the disease is symptomatic. The various means of hormonal treatment (surgical castration, LH-RH agonists, anti-androgens) should be considered with regard to the status of the patient, the manifestations of cancer and potential side effects of treatment. Surgery and/or radiation therapy is indicated for symptomatic relief in treatment of local dissemination (extension to the urinary tract, etc.) or bone metastases. In case of hormonal treatment failure, no other treatment is really effective, and survival is short. Symptomatic treatments are then used to increase quality of life.

Adenocarcinoma↗

PubMed2004

HOXB13 induces growth suppression of prostate cancer cells as a repressor of hormone-activated androgen receptor signaling.

Androgen receptor (AR) signals play a decisive role in regulating the growth and differentiation of both normal and cancerous prostate cells by triggering the regulation of target genes, in a process in which AR cofactors have critical functions. Because of the highly prostate-specific expression pattern of HOXB13, we studied the role of this homeodomain protein in prostate cells. Expression of HOXB13 was limited to AR-expressing prostate cells. Reporter transcription assay demonstrated that HOXB13 significantly suppressed hormone-mediated AR activity in a dose-responsive manner, and suppression was specific to AR with which HOXB13 physically interacts. Overexpression of HOXB13 further down-regulated the androgen-stimulated expression of prostate-specific antigen, and suppression of endogenous HOXB13 stimulated transactivation of AR. Functionally, HOXB13 suppressed growth of LNCaP prostate cancer cells, which could be counteracted by additional hormone-activated AR. On the other hand, the growth-suppressive function of HOXB13 in AR-negative CV-1 cells was not affected by AR. These results suggest that HOXB13 functions as an AR repressor to modulate the complex AR signaling and subsequent growth regulation of prostate cancer cells. In addition to the loss of HOXB13 expression, maintaining AR may be an important step for prostate cancer cells to tolerate the suppressor function of HOXB13. Altogether, our data present a novel mechanism for the HOXB13-mediated repression of AR signaling, which can be interpreted to a growth-suppressive event.

Androgen Receptor Antagonists↗

PubMed2003

Expression of the human cachexia-associated protein (HCAP) in prostate cancer and in a prostate cancer animal model of cachexia.

Prostate cancer (CaP) patients with disseminated disease often suffer from severe cachexia, which contributes to mortality in advanced cancer. Human cachexia-associated protein (HCAP) was recently identified from a breast cancer library based on the available 20-amino acid sequence of proteolysis-inducing factor (PIF), which is a highly active cachectic factor isolated from mouse colon adenocarcinoma MAC16. Herein, we investigated the expression of HCAP in CaP and its potential involvement in CaP-associated cachexia. HCAP mRNA was detected in CaP cell lines, in primary CaP tissues and in its osseous metastases. In situ hybridization showed HCAP mRNA to be localized only in the epithelial cells in CaP tissues, in the metastatic foci in bone, liver and lymph node, but not in the stromal cells or in normal prostate tissues. HCAP protein was detected in 9 of 14 CaP metastases but not in normal prostate tissues from cadaveric donors or patients with organ-confined tumors. Our Western blot analysis revealed that HCAP was present in 9 of 19 urine specimens from cachectic CaP patients but not in 19 urine samples of noncachectic patients. HCAP mRNA and protein were also detected in LuCaP 35 and PC-3M xenografts from our cachectic animal models. Our results demonstrated that human CaP cells express HCAP and the expression of HCAP is associated with the progression of CaP and the development of CaP cachexia.

Animals↗

PubMed1999

Assessing the risk of unsuspected prostate cancer in patients with benign prostatic hypertrophy: a 13-year retrospective study of the incidence and natural history of T1a-T1b prostate cancers.

OBJECTIVE: To determine the incidence and natural history of stage T1a-T1b prostate cancer in patients undergoing surgery for benign prostatic hypertrophy (BPH), and thus evaluate the effect that recent medical and 'minimally invasive' treatments (which provide no prostate sample for pathological examination) might have on the percentage of patients with unsuspected prostate cancer. PATIENTS AND METHODS: A series of 1648 patients undergoing surgery for BPH over a 13-year period were reviewed retrospectively; the period overlapped the introduction of serum prostate specific antigen (PSA) as a detection method. RESULTS: Stage T1 prostate cancer was found in 182 patients (11%), comprising 126 (11%) of 1199 transurethral resections and 56 (12%) of 449 open enucleations. The introduction of systematic PSA assays gradually reduced the mean incidence of T1 cancer from 23% to 7%, with a greater effect on T1b (from 15% to 2%), while the incidence of T1a remained nearly constant (+/-5%). The pathological features of surgical specimens from 43 radical prostatectomies undertaken for T1 tumours were reviewed. Locally advanced disease (stage >/=pT3) was apparent in 13% of T1a and 28% of T1b tumours. Amongst the patients electing for surveillance, only 8% of those with T1a progressed within 30-97 months of follow-up (mean progression time 73 months), whereas 29% of those with stage T1b progressed within 36 months of follow-up (mean progression time 17 months). CONCLUSION: These results show that the use of the PSA assay has decreased but not suppressed the incidence of pT1 prostate cancer, with a greater effect on those tumours at higher risk of progression (T1b). This suggests that the detection of prostate cancer based on PSA and transrectal ultrasonography is appropriate for screening patients and is sufficiently accurate that treatments for BPH that provide no pathological materials can be applied safely.

Aged↗

PubMed1999

Detection of subclinical cancers by prostate-specific antigen screening in asymptomatic men from high-risk prostate cancer families.

Positive family history is a significant risk factor for prostate cancer. Improved knowledge of the epidemiology and molecular basis of hereditary prostate cancer has led to a need for counseling and clinical follow-up for men with a positive family history of prostate cancer. However, very little information is available on the efficacy of early screening procedures, such as serum prostate-specific antigen (PSA) measurements, in the management of genetically predisposed, high-risk individuals. In a nationwide study, we obtained family histories from 2099 Finnish prostate cancer patients and identified 302 families with two or more affected cases. Here, 209 asymptomatic 45-75-year-old males from these families were included in a study to determine the frequency of serum PSA positivity and the prevalence of subclinical prostate cancers. Serum PSA was elevated in 21 (10.0%) of these high-risk individuals. Seven prostate cancers (3.3%) and two high-grade prostatic intraepithelial neoplasia lesions were diagnosed, with three cancers occurring in men ages < or = 59 years. Men from prostate cancer families with an average age of onset of < 60 years had a significantly higher frequency of PSA positivity (28.6%, P = 0.01) as well as cancers (14.3%, P = 0.02) than those with a later age of onset. The results suggest that prostate cancer development in genetically predisposed individuals is preceded by a subclinical period when PSA detection is possible. Serum PSA screening may be particularly useful in men with a family history of early-onset prostate cancer.

Adenocarcinoma↗

PubMed2005

Selenium level in benign and cancerous prostate.

The dietary microelement selenium (Se) has been proposed as a potential chemopreventive agent for prostate cancer. This element is present in various amounts in all tissues. Little information is available on Se level in patients with prostate gland disorders. The levels of Se in prostatic gland of patients with prostate cancer, benign prostate hyperplasia, and healthy controls were examined. The Se level for benign prostate hyperplasia (156 +/- 30.6 ng/g) was the same as in the control group (157 +/- 26.0 ng/g), but in the gland of prostate cancer patients (182 +/- 34.1 ng/g wet weight), the Se level was significantly (p < 0.01) higher than in both healthy controls and benign prostate hyperplasia. Thus, the Se level in human healthy controls is lower than in kidney and liver but higher compared with other tissues.

Aged↗

PubMed1997

No germline mutations in the dimerization domain of MXI1 in prostate cancer clusters. The CRC/BPG UK Familial Prostate Cancer Study Collaborators. Cancer Research Campaign/British Prostate Group.

There is evidence that predisposition to cancer has a genetic component. Genetic models have suggested that there is at least one highly penetrant gene predisposing to this disease. The oncogene MXI1 on chromosome band 10q24-25 is mutated in a proportion of prostate tumours and loss of heterozygosity occurs at this site, suggesting the location of a tumour suppressor in this region. To investigate the possibility that MXI1 may be involved in inherited susceptibility to prostate cancer, we have sequenced the HLH and ZIP regions of the gene in 38 families with either three cases of prostate cancer or two affected siblings both diagnosed below the age of 67 years. These are the areas within which mutations have been described in some sporadic prostate cancers. No mutations were found in these two important coding regions and we therefore conclude that MXI1 does not make a major contribution to prostate cancer susceptibility.

Adult↗

PubMed2005

[Ultrasound contrast agents and prostate cancer].

Prostatic carcinoma is the most frequent malignant disease in men and associated with very high mortality. The diagnostic work-up of prostatic carcinoma is based on tests to determine the level of prostate-specific antigen (PSA), digital rectal examination, and transrectal sonography. Due to diagnostic limitations, ultrasound-guided prostate biopsy is the method of choice for diagnosis of prostatic carcinoma. New imaging technologies allow detection of prostatic carcinoma, thus facilitating removal of specific biopsy specimens from these regions. Introduction of ultrasound contrast agents ("echo signal enhancers") significantly increased the diagnostic potential of this method, making it possible to visualize tumor vascularization.

Biopsy↗

PubMed1992

Histologic features of metastatic prostate cancer.

Prostate carcinomas begin as well-differentiated lesions. Before metastases occur these carcinomas dedifferentiate into moderately or poorly differentiated lesions and increase in size to at least 1 cm3. Well-differentiated lesions rarely metastasize and metastases are rarely well differentiated. Positive staging lymphadenectomies usually contain moderately differentiated metastases. Patients with moderately differentiated metastases have a statistically significant better survival than patients with poorly differentiated metastases. Metastases typically disseminate as they dedifferentiate, with stage D1 metastases being moderately differentiated and stage D2 metastases being poorly differentiated. "Prostate-specific" immunohistochemical techniques and serum prostate-specific antigen levels may be helpful in determining whether a particular metastases is from the prostate. However, metastases of uncertain origin should rarely, if ever, be attributed to the prostate without confirmation that the patient has a prostate carcinoma with histologic features capable of metastasizing.

Adenocarcinoma↗

PubMed2006

Image-guided brachytherapy for prostate cancer.

Prostate brachytherapy offers and effective treatment for organ-confined prostate carcinoma. It is rapidly delivered compared with external beam radiation therapy or surgery and well tolerated by patients. Volumetric imaging and image guidance play critical roles in patient selection, treatment planning, treatment delivery, and postimplant assessment. Costs, availability and ease of use often dictate the local and regional differences in imaging approach, whether ultrasound, CT, or MR. Future volumetric image developments may permit multimodality image fusion to integrate tumor-specific imaging such as MR spectroscopy or positron emission tomography/CT into real-time ultrasound, CT, or MR.

Brachytherapy↗

PubMed1987

Prospective comparison between serum monoclonal prostate specific antigen and acid phosphatase measurements in metastatic prostatic cancer.

Prostate specific antigen, prostatic acid phosphatase antigen and acid phosphatase activity were measured on 175 serum samples serially collected from 80 patients with metastatic stage D adenocarcinoma of the prostate. Prostate specific antigen and prostatic acid phosphatase antigen concentrations were measured with a monoclonal radioimmunometric assay, and acid phosphatase activity was measured enzymatically. The over-all frequency of abnormal levels of prostate specific antigen (76 per cent) was significantly greater than abnormal prostatic acid phosphatase antigen (60 per cent) and acid phosphatase activity (49 per cent) results (p less than 0.001). These differences were greater among the subset of patients in clinical remission. Levels greater than 10 times normal were observed in 68 per cent of prostate specific antigen, 43 per cent of prostatic acid phosphatase antigen and 31 per cent of acid phosphatase activity measurements (p less than 0.001). Three or more serial prostate specific antigen measurements in 17 patients demonstrated excellent correlation with independently assessed clinical disease activity. These results suggest that prostate specific antigen is a more sensitive and potentially more useful tumor marker than acid phosphatase measurements in patients with metastatic prostatic carcinoma.

Acid Phosphatase↗

PubMed1999

Permanent radioactive seed implantation in the treatment of prostate cancer.

Prostate brachytherapy has come a long way in the last 15 years, from an open free-hand technique with which seed placement was often inaccurate to the highly technical and accurate procedure of today. It has become a viable treatment option for low-risk patients along with EBRT and prostatectomy. Its most promising use may be in combination with hormonal therapy and EBRT in moderate- to high-risk patients, for whom it may offer improved outcomes over standard single-modality therapies.

Brachytherapy↗

PubMed2004

In silico dissection of cell-type-associated patterns of gene expression in prostate cancer.

Prostate tumors are complex entities composed of malignant cells mixed and interacting with nonmalignant cells. However, molecular analyses by standard gene expression profiling are limited because spatial information and nontumor cell types are lost in sample preparation. We scored 88 prostate specimens for relative content of tumor, benign hyperplastic epithelium, stroma, and dilated cystic glands. The proportions of these cell types were then linked in silico to gene expression levels determined by microarray analysis, revealing unique cell-specific profiles. Gene expression differences for malignant and nonmalignant epithelial cells (tumor versus benign hyperplastic epithelium) could be identified without being confounded by contributions from stroma that dominate many samples or sacrificing possible paracrine influences. Cell-specific expression of selected genes was validated by immunohistochemistry and quantitative PCR. The results provide patterns of gene expression for these three lineages with relevance to pathogenetic, diagnostic, and therapeutic considerations.

Gene Expression Profiling↗

PubMed1999

Phosphorus balance and prostate cancer.

Prostatic diseases affect men over the age of 45 and increase in frequency with age so that by the eighth decade more than 90% of men have Benign Prostatic Hyperplasia, (BPH), of which some progress to Carcinoma of Prostate (CaP). CaP, the most common malignancy in men, is also the second most common cause of death in men. Over the last three decades the mortality rate for CaP has steadily increased. There, however, are scant clues to the aetiology/pathogenesis of CaP. As treatment failures of advanced carcinoma continue to frustrate clinicians, emphasis has recently been focused on possible preventive strategies. Several studies support the view that higher levels of 1,25-(OH)2D, the active metabolite of vitamin D, reduce the risk of BPH and CaP. Men with high serum levels of 1,25-(OH)2D have a reduced risk of poorly differentiated and clinically advanced CaP. Hypercalcemic activity of 1,25-(OH)2D or its analogues, however, thwart their use for therapy in humans. Incidentally, a low dietary intake of phosphorus has been reported to increase serum levels of 1,25-(OH)2D. In addition, dietary fructose reduces plasma phosphate levels by 30 to 50% for more than 3 hr. Fruit intake has, indeed, been shown to be associated with reduced risk of CaP, particularly the advanced type. These observations, taken together, support that dietary determinants of hypophosphatemia, leading to increased plasma levels of 1,25-(OH)2D, could reduce the risk of ageing men to develop prostatic diseases, both BPH and/or carcinoma of Prostate.

Humans↗

PubMed2000

Screening for prostate cancer using prostate-specific antigen alone as a first-line checkup parameter: results of the health checkup system.

BACKGROUND: The incidence of prostate cancer in Japan is not very high but it is the most increasing malignant tumor form. To decrease the mortality from cancer, detection of early cancer and early treatment are most effective. As a primary screening for prostate cancer, measurement of serum prostate-specific antigen(PSA) added to the health checkup system has not been assessed. METHODS: Among males who received a health checkup during a 30-month period, serum PSA levels were measured in males who desired prostate cancer screening. The cut-off value for PSA was 4.0 ng/ml. Males with serum PSA levels exceeding this value were referred for further screening by digital rectal examination (DRE) and transrectal ultrasonography (TRUS). In secondary screening, in all males with PSA levels of 10.0 ng/ml or more and in males in whom PSA levels were within the gray zone (4.0-10.0 ng/ml) and either DRE or TRUS showed abnormal findings, systematic prostate sextant needle biopsy was performed. RESULTS: Of 24528 males who received a health checkup, 1125 (4.6%) underwent prostate cancer screening. In 60 (5.3%) of these males, PSA levels exceeded the cut-off value. In 34 of 50 males who received further screening, prostate biopsy was performed. Seventeen males were diagnosed as having prostate cancer. Detection rates of prostate cancer were 1.53% (17/1125) in males overall and 2.1% (17/819) in males > or =50 years old. In 16 of 17 males, clinically localized cancer was suggested. In 12 of these patients, radical prostatectomy was performed. No lymph node metastasis was detected in any patient. CONCLUSIONS: These results suggest that prostate cancer screening using PSA as a primary screening parameter during general health checkups is very useful for efficiently detecting early-stage prostate cancer.

Aged↗

PubMed2001

[Predictive value of prostate specific antigen density in the detection of prostate cancer in patients with elevated prostate specific antigen levels and normal digital rectal findings or stage A prostate cancer].

We compared the usefulness of PSA and PSA density (PSAD) in diagnosing prostate cancer in 102 men who had a PSA value higher than 4.0 ng/ml and normal digital rectal examination and who had undergone transrectal ultrasonography-guided systematic sextant biopsies of the prostate between August 1996 and October 1999. In addition, for a group of 53 patients who underwent retropubic simple prostatectomy, PSA, PSAD and PSA transition zone (PSA-TZ) examination results for those with stage A prostate cancer were compared with the results for those with benign prostatic hyperplasia (BPH). Of the former 102 men, 20 (19.6%) had prostate cancer. There was no significant difference in mean PSA level between patients with negative and those with positive biopsy results (mean 9.3 and 11.8, respectively, p = 0.295), but the mean PSAD of patients with positive biopsy results was significantly higher than that of those with negative results (mean 0.55 and 0.29, respectively, p = 0.0007). Of the 53 men who underwent retropubic simple prostatectomy, 10 (18.9%) were diagnosed with stage A prostate cancer. There was no significant difference in mean PSA, PSAD and PSA-TZ examination results between patients with BPH and those with stage A prostate cancer. For all 102 patients and for 71 patients with PSA levels of 4.1-10.0 ng/ml, a PSAD cutoff value of 0.1 reduced the number of biopsies 15.7% (16 of 102 cases), and 22.5% (16 of 71 cases), respectively. These results suggest that by measurement of PSAD some patients with benign disease could be spared a biopsy which would have been performed based on PSA results alone.

Aged↗

PubMed2003

Differentiation of prostate cancer and benign prostatic hyperplasia: the clinical value of 201Tl SPECT--a pilot study.

PURPOSE: Thallium-201 (201Tl) is a recognized tumor-imaging agent; however, the usefulness of 201Tl in prostate cancer has not been studied. The purpose of this preliminary study was to evaluate the efficacy of 201Tl single-photon emission computed tomography (SPECT) imaging for differentiating prostate cancer from benign prostatic hyperplasia (BPH). METHODS: 201Tl pelvic SPECT was performed in 10 patients (aged 64-78 years) with biopsy-proven BPH before transurethral resection of the prostate and 15 patients (aged 65-81 years) with biopsy-proven prostate cancer prior to any therapeutic modality or invasive surgical procedures for treatment of their prostate cancer. RESULTS: From the 15 patients with prostate cancer, 201Tl pelvic SPECT detected prostate cancer in 13 (86.7%) but not in 2 (13.3%) patients with Gleason scores of 5 (2 + 3). In contrast, all 10 patients with BPH (100.0%) had negative results of 201Tl pelvic SPECT. CONCLUSION: Our study showed that 201Tl pelvic SPECT scan is very helpful in distinguishing between prostate cancer and BPH.

Aged↗