[Countermeasure against prostate cancer with advanced age].
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Age Factors↗
Biomedical subjects
Kazuto Ito
Publications and source records attributed to Kazuto Ito.
[Chronological changes of incidence rates, clinical stages and pathological differentiation of prostate cancer in Gunma Prefecture, Japan].
Prostate cancer is the most common urogenital cancer, and is increasing rapidly. We performed an epidemiological study on prostate cancer in Gunma Prefecture, Japan. Registration of prostate cancer patients diagnosed at clinics and hospitals in and around Gunma Prefecture was started at Gunma University in 1985. The epidemiological characteristics of prostate cancer patients in Gunma Prefecture were analyzed by these data. The incidence and crude incidence rates have increased five-fold, from 114 and 12.0 in 1985 to 539 and 53.9 in 2000, respectively. The age-adjusted incidence rate (adjusted to the world population) was increased three-fold, from 8.3 in 1985 to 24.2 in 2000. The age-specific incidence rate showed an increase with age. The cancers in clinical stages A and D decreased, while those in stages B and C increased. No change in distribution was observed in pathological differentiation. Prostate cancer has increased rapidly during these 16 years in Gunma Prefecture. It is important to perform PSA testing aggressively in males age 50 or older, and detect prostate cancer in an early stage.
Age Factors↗
[Advancements in PSA-based screening for prostate cancer].
As the most frequently diagnosed cancer and the second leading cause of cancer death in most Western countries, prostate cancer represents a significant health care problem. The introduction of routine prostate-specific antigen (PSA) screening for asymptomatic men is still controversial. To solve uncertainties regarding the screening for prostate cancer, prospective randomized controlled trials are ongoing in the USA and Europe. The development of an optimal screening system may be one of the most important issues for screening for prostate cancer, and it should be set not only for reducing the mortality rate of prostate cancer, but also for reducing the cost. The best screening modality for the 1st step of mass screening for prostate cancer is the PSA test. Furthermore, the cut-off value should be set in an age-specific manner. The risk of developing prostate cancer in men with PSA levels of 4.0 ng/ml or lower increases when the baseline PSA levels are higher. Therefore, re-screening for men without suspicious findings for prostate cancer at the 1st step of screening should be set relative to the baseline PSA and digital rectal examination status. In the 2nd step of screening, the PSA density adjusted by the transition zone volume (PSATZD) and free/total PSA ratio (%f-PSA) may be useful in the selecting patients who should be biopsied. The optimal cut-offs for PSATZD and %f-PSA have not been confirmed, however, and an age-adjusted setting should be considered to detect clinically significant cancer. The method of prostate biopsy is also very important for improving the diagnostic accuracy for prostate cancer. The number of biopsy cores should be set relative to prostate volume. Furthermore, the clinically significant tumor volume may be smaller in younger men than in older men. Therefore, the optimal number of biopsy cores should be set according to age and prostate volume. Both an optimal screening system and minimally invasive treatments will be available in the future, and screening for prostate cancer may be more useful for elderly males.
Age Distribution↗
Regulation of metallothionein and zinc transporter expression in human prostate cancer cells and tissues.
Prostate glands contain heavy metals such as zinc and cadmium, and epidemiological studies showed that both metals were associated with prostate cancer development. To understand the heavy metal metabolism in prostate glands, we investigated the regulation of metallothionein (MT), metal-responsive promoter element-binding transcription factor (MTF) and zinc transporter (ZnT) in human prostate cells and tissues. Growth of human prostate cancer cells, LNCaP and PC-3 cells, was suppressed by zinc or cadmium treatment in a dose-dependent manner. LNCaP cells expressed MT-1A, 1X and 2A mRNA, and PC-3 cells expressed MT-1X and 2A mRNA. Zinc or cadmium treatment up-regulated MTs, MTF-1 and ZnT-1 gene expression levels in both cell lines. In PC-3 cells, ZnT-1 protein was detected, and was up-regulated by the metal treatment. Human prostate cancer tissues expressed significantly lower levels of ZnT-1 gene in comparison with hyperplastic tissues. We demonstrated the ZnT-1 expression in human prostate for the first time. The present study showed that heavy metal-metabolizing proteins were involved in human prostate homeostasis, and that the metal metabolizing system might be different in malignant tissues.
Cadmium↗
Genetic polymorphisms of estrogen receptor alpha, CYP19, catechol-O-methyltransferase are associated with familial prostate carcinoma risk in a Japanese population.
BACKGROUND: Estrogen is one of the crucial hormones participating in the proliferation and carcinogenesis of the prostate glands. Genetic polymorphisms in the estrogen metabolism pathway might be involved in the risk of prostate carcinoma development. The authors evaluated the association between genetic polymorphisms in estrogen-related enzymes and receptors and the risk of developing familial prostate carcinoma. METHODS: In the current study, 101 cases with prostate carcinoma whose first-degree relatives had prostate carcinoma and 114 healthy age and residence-matched male controls were enrolled. The genotypes of estrogen receptor (ER) alpha, aromatase (CYP19), and catechol-O-methyltransferase (COMT) genes were analyzed. RESULTS: For single polymorphisms, a significant association of the T/T genotype of the PvuII site in the ER alpha gene (odds ratio [OR], 3.44; 95% confidence interval [CI], 1.97-5.99; P = 0.0028), and the C/T and T/T genotypes of the CYP19 gene (OR, 1.77; 95% CI, 1.02-3.09; P = 0.037) with prostate carcinoma risk, was observed. The G/A genotype of the COMT gene showed a weak tendency toward increased risk (OR, 1.48; 95% CI, 0.85-2.57; P = 0.18). Stratification of cases according to clinical stage and pathologic grade showed that the C/T and T/T genotypes of the CYP19 gene were associated significantly with high-grade carcinoma (OR, 2.59; 95% CI, 1.47-4.46; P = 0.048). The number of high-risk genotypes (the T/T in ER alpha, the C/T and T/T in CYP19, and the G/A in COMT) significantly increased the risk of developing prostate carcinoma (2 genotypes: OR, 3.00; 95% CI, 1.72-5.23; P = 0.008; 3 genotypes: OR, 6.30; 95% CI, 3.61-10.99; P = 0.002). CONCLUSIONS: Genetic polymorphisms of genes in the estrogen metabolism pathway were associated significantly with familial prostate carcinoma risk. Single nucleotide polymorphisms of low-penetrance genes are targets for understanding the genetic susceptibility of familial prostate carcinoma.
Adult↗
Possibility of re-screening intervals of more than one year in men with PSA levels of 4.0 ng/ml or less.
BACKGROUND: The optimal re-screening interval is one of the most important issues to evaluate the effectiveness of screening for prostate cancer. METHODS: Between 1992 and 2000, 7,026 men aged 50-78 with baseline PSA levels of 4.0 ng/ml or lower underwent screening for prostate cancer twice or more. The risk of developing prostate cancer relative to elapsed years and baseline PSA levels were investigated. RESULTS: Prostate cancer was detected in a total of 127 cases (1.8%). The detection rate of prostate cancer was high between 1.6% and 5.5% at 1 year after baseline PSA measurements in men with baseline PSA levels of 2.1-4.0 ng/ml. In men with baseline PSA levels of 1.1- 2.0 ng/ml, the detection rate increased from 0.06% to 1.02% with passed years. The proportion of stage >/=T3 was high at 63% in prostate cancer cases detected between 3 and 4 years after baseline PSA levels being 1.1-2.0 ng/ml. In men with baseline PSA levels of 1.0 or lower, the cumulative detection rate of prostate cancer was low at 0.01% within 3 years, however, the detection rate increased to 0.34% after 5 or more years from baseline PSA measurements. CONCLUSIONS: The re-screening interval was recommended to be 1, 1-2, and 3-5 years for men with baseline PSA levels of 2.1-4.0 ng/ml, 1.1-2.0 ng/ml, and 1.0 ng/ml or lower, respectively.
Aged↗
Association of the genetic polymorphism in cytochrome P450 (CYP) 1A1 with risk of familial prostate cancer in a Japanese population: a case-control study.
Association between genetic polymorphisms of CYP1A1 and familial prostate cancer risk was examined by a case-control study of 185 individuals. Although the individual analysis of m1 or m2 genotype of CYP1A1 showed no significant association with prostate cancer risk, the presence of any mutated alleles significantly increased prostate cancer risk in comparison with wild-type genotypes by combination analysis (odds ratio [OR]=2.38; 95% confidence interval [CI]=1.72-3.29; P=0.0069). Furthermore, metastatic cancer had a significant association with mutated alleles of m1 and m2. These finding suggested that CYP1A1 polymorphisms has an association with prostate cancer risk, especially with progression of prostate cancer.
Adenocarcinoma↗
Informed consent for prostate-specific antigen-based screening--European view.
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Europe↗
Free/total PSA ratio is a powerful predictor of future prostate cancer morbidity in men with initial PSA levels of 4.1 to 10.0 ng/mL.
OBJECTIVES: To evaluate the usefulness of measuring the free/total prostate-specific antigen (PSA) ratio (%fPSA) in men with initial PSA levels of 4.1 to 10.0 ng/mL as a predictor of the future risk of developing prostate cancer. METHODS: Between 1989 and 2001, 201 subjects with an initial PSA level of 4.1 to 10.0 ng/mL, who had free PSA measured at initial screening using frozen serum and underwent consecutive screening at least once, were enrolled in this study. All participants were followed up by consecutive PSA measurements. Biopsies were performed for those with PSA levels greater than 10.0 ng/mL or with a PSA velocity of 1.0 ng/mL or greater in consecutive screening. The follow-up period was 1 to 12 years, and the mean number of screenings was 3.8. The usefulness of %fPSA, age, and total PSA as predictive factors of future prostate cancer morbidity was investigated. The cumulative non-prostate cancer rate was evaluated using Kaplan-Meier analysis relative to various %fPSA cutoffs. RESULTS: A total of 142 patients (71%) underwent prostate biopsy at least once during observation according to the biopsy criteria. The detection rate of prostate cancer was 26% (53 of 201) in consecutive screening. The most recent PSA velocity and serum PSA levels at last follow-up in patients with prostate cancer were significantly higher than in those without prostate cancer. The cumulative non-prostate cancer rate was significantly greater in subjects with %fPSA less than the cutoff than in those with %fPSA at the cutoff point or greater in the %fPSA cutoffs of 16% to 25%. CONCLUSIONS: Men with PSA levels of 4.1 to 10 ng/mL who are not suspected of having prostate cancer by whatever means should undergo %fPSA measurement and be carefully monitored at short intervals over the long-term if they have lower %fPSA levels.
Aged↗
Natural history of PSA increase with and without prostate cancer.
OBJECTIVES: To investigate the natural history of prostate-specific antigen (PSA) increase in men with and without prostate cancer to clarify the probability of cancer-related PSA increase. METHODS: Between 1986 and 2001, 504 men aged 79 years or younger with baseline PSA levels of 4.0 ng/mL or less and a PSA increase greater than 4.0 ng/mL on consecutive screening were enrolled in this study. The types of PSA increase were classified as "non-cancer-related PSA increase," "suspicious cancer-related PSA increase," and "cancer-related PSA increase." The probability of a "cancer-related PSA increase" was investigated and stratified by baseline PSA levels and elapsed years until the PSA level increased to greater than 4.0 ng/mL. RESULTS: The probability of a "non-cancer-related increase," "suspicious cancer-related PSA increase," and "cancer-related PSA increase" was 57%, 15%, and 28%, respectively. The PSA velocity before the PSA increase was not significantly different between those with and without prostate cancer. A "non-cancer-related PSA increase" was observed in 92% of those with a PSA increase within 2 years of baseline PSA ranges of 2.0 ng/mL or less. Regardless of elapsed years until a PSA increase to greater than 4.0 ng/mL, a "suspicious cancer-related PSA increase" or "cancer-related PSA increase" was observed in almost one half of those with baseline PSA levels of 2.1 to 4.0 ng/mL. CONCLUSIONS: Intensive serial observations should be recommended before undergoing biopsy for those with a PSA increase within 2 years of a baseline PSA range of 0.0 to 2.0 ng/mL. It may be difficult to distinguish between those with and without cancer using only subsequent total PSA measurements for the remaining cases, and prostate biopsy should be recommended at present.
Adenocarcinoma↗
Preliminary results of a monitoring system to confirm the preservation of cavernous nerves.
BACKGROUND: It is important to preserve the neurovascular bundle (NVB) during nerve-sparing surgery. This article presents the preliminary results of our monitoring system for the postoperative preservation of erectile function. METHODS: In 15 patients undergoing radical prostatectomy and 20 patients undergoing radical cystoprostatectomy, intraoperative electrical stimulation along the NVB was performed to measure changes in intracavernous pressure before and after prostate removal. Seven of the radical prostatectomy patients and eight of the radical cystoprostatectomy patients underwent nerve-sparing surgery. Postoperative erectile function was evaluated in 25 patients not receiving adjuvant hormonal therapy. RESULTS: The NVB was judged to be preserved at least on one side electrophysiologically in 14 of 15 patients. Pathologically, three patients had pT3 cancer. Postoperatively, sufficient erectile function was demonstrated using the International Index of Erectile Function 5 in three patients, nocturnal penile tumescence in three patients, and a questionnaire or an interview in three patients. The other patients were incompletely erectile. None of the 11 patients not receiving adjuvant hormonal therapy, in whom NVB was not preserved, were erectile. CONCLUSION: If the successful criterion of nerve-sparing surgery is defined as a change in intracavernous pressure of 4 cm H2O or more being observed at least unilaterally, and the successful criteria of erectile function preservation includes being sufficiently erectile as revealed by an interview, the sensitivity of our system was 69.2% (9/13) and the specificity was 100% (12/12). Neither adverse reactions to the measurement, nor inadequacy of cancer excision accompanying NVB sparing, were observed. These results suggest that our system can predict postoperative erectile function fairly accurately.
Aged↗
The diagnostic accuracy of the age-adjusted and prostate volume-adjusted biopsy method in males with prostate specific antigen levels of 4.1-10.0 ng/mL.
BACKGROUND: The authors evaluated a new age-adjusted and prostate volume-adjusted biopsy method for the detection of prostate carcinoma through the transperineal and the transrectal approaches in men with PSA levels of 4.1-10.0 ng/mL. METHODS: The value of the adjusted biopsy method was calculated by using the following four factors: 1) life expectancy in Japanese men in 1998, 2) prostate volume estimated by transrectal ultrasonography, 3) tumor doubling time (4 years), and 4) tumor volume that influenced death (20 cc). The number of biopsy sites was set at 8-20. Between August, 1999 and December, 2001, 100 men age or= 50 cc, and men with PSA density (PSAD) levels /= 50 cc), and patients with PSAD levels <or= 0.15 ng/mL/cc. The authors recommend that patients undergo an additional transition zone biopsy at the anterior aspect through the transperineal approach.
Age Factors↗
Genistein, a soy isoflavone, induces glutathione peroxidase in the human prostate cancer cell lines LNCaP and PC-3.
Genistein is a major component of soybean isoflavone and has multiple functions resulting in antitumor effects. Prostate cancer is 1 of the targets for the preventive role of genistein. We examined the effect of genistein on human prostate cancer (LNCaP and PC-3) cells. Proliferation of both cell lines was inhibited by genistein treatment in a dose-dependent manner. To obtain the gene expression profile of genistein in LNCaP cells, we performed cDNA microarray analysis. The expression of many genes, including apoptosis inhibitor (survivin), DNA topoisomerase II, cell division cycle 6 (CDC6) and mitogen-activated protein kinase 6 (MAPK 6), was downregulated. Expression levels were increased more than 2-fold in only 4 genes. The glutathione peroxidase (GPx)-1 gene expression level was the most upregulated. Quantitative real-time polymerase chain reaction revealed significant elevation of transcript levels of GPx-1 in both LNCaP and PC-3 cells. Upregulation of gene expression levels accompanied elevation of GPx enzyme activities. In contrast, no significant changes were observed in the gene expression levels and enzyme activities of the other antioxidant enzymes, superoxide dismutase and catalase. GPx activation might be one of the important characteristics of the effects of genistein on prostate cancer cells.
Antineoplastic Agents↗
Effectiveness of mass screening for the prognosis of prostate cancer patients in Japanese communities.
BACKGROUND: A study was conducted to investigate the effectiveness of mass screening (MS) for prostate cancer in Japanese communities using the long-term follow-up results. METHODS: Subjects were 279 patients with prostate cancer detected by MS in Gunma prefecture (MS group) and 624 patients with prostate cancer who did not undergo screening (non-MS group). From the follow-up data, the prognoses were compared between the groups. RESULTS: The ratio of patients with Stage II cancer was higher for the MS group (59.1%) when compared to non-MS group (25.3%). As a whole, the prognosis of the MS group was more favorable than that of the non-MS group for relative survival rate. Prognosis was especially favorable for patients with Stage III prostate cancer in mass screening group considering the effect of lead-time bias. CONCLUSIONS: Early detection and longer survival of the patients with prostate cancer detected by mass screening suggested the effectiveness of prostate cancer screening.
Age Factors↗
Usefulness of PSA screening in outpatients with bladder cancer: preliminary results.
BACKGROUND: We performed prostate-specific antigen (PSA) screening and evaluated its usefulness in outpatients with bladder cancer who may have an elevated risk for prostate cancer. METHODS: Sixty-one new or followed-up outpatients with bladder cancer were examined between September 1999 and December 2000 in the Department of Urology, Gunma University Hospital, Japan. PSA was measured after informed consent was obtained, and patients in whom the PSA level was 4.1 ng/mL or higher were selected for thorough examination. In the examination, one examiner performed DRE (digital rectal examination) and, based on DRE and TRUS (transrectal ultrasonography) findings, determined whether prostate biopsy was indicated. RESULTS: The average age of the 61 cases was 69.1 +/- 8.6 years, and the average PSA level was 3.5 +/- 5.8 ng/mL. The PSA level was 4.1 ng/mL or higher in 11 (18.0%) patients, nine of whom underwent six-sextant biopsy under TRUS guidance. Of these nine cases, four (6.6%) were diagnosed as having prostate cancer. The Gleason score was 7 in three cases and 9 in one case. The clinical stage was T2N0M0 in three cases and T3N0M0 in one case. CONCLUSIONS: On PSA screening in patients with bladder cancer and patients with a history of transurethral resection of the bladder tumor (TUR-BT), prostate cancer was found in 6.6%. This rate is higher than in the general population. These cancers were classified into intermediate to high-risk groups, and the prognosis of prostate cancers could be more important than those of the bladder cancers in two cases (50%). We conclude that PSA screening for inpatients with bladder cancer may be useful.
Aged↗
Usefulness of prostate-specific antigen velocity in screening for prostate cancer.
BACKGROUND: The cut-off value of prostate-specific antigen velocity (PSAV) was investigated in relation to the initial prostate-specific antigen (PSA) value in subjects with initial values of 1.0-4.0 ng/mL, and the usefulness and limitations of PSAV as a screening test for prostate cancer were examined. METHODS: In this study, 4883 men who underwent mass screening for prostate cancer two or more times between 1987 and 1998 and had initial PSA levels of 1.0-4.0 ng/mL were investigated. The subjects ranged in age from 42 to 96 years (mean: 68.0 +/- 6.6 years). The cut-off value of PSAV was set at 0.1-1.5 ng/mL per year, and the sensitivity, specificity, efficiency and positive predictive value (PPV) of PSAV for detecting prostate cancer were determined according to the initial PSA value. A similar examination of the average PSAV was carried out in 2888 subjects with three or more visits for mass screening for prostate cancer. RESULTS: The diagnostic efficiency of PSAV was optimal with cut-off values of 0.3 and 0.75 ng/mL per year in those subjects with initial PSA levels of 1.0-1.9 and 2.0-4.0 ng/mL, respectively, but the PPV was low at 1.8% in subjects with initial PSA levels of 1.0-1.9 ng/mL. When the cutoff value of PSAV was set at 1.2 ng/mL per year in individuals with initial PSA levels of 1.0-1.9 ng/mL, the PPV increased to 7.3% and the sensitivity was 40%. The diagnostic efficiency of the average PSAV was optimal at the cut-off values of 0.2 and 0.4 ng/mL per year in subjects with initial PSA levels of 1.0-1.9 and 2.0-4.0 ng/mL, respectively, but the PPV was low at 2.2% in the subjects with initial PSA values of 1.0-1.9 ng/mL. When the cut-off value of PSAV was set at 0.75 ng/mL per year in individuals with initial PSA levels of 1.0-1.9 ng/mL, the PPV was 9.8% and the sensitivity was 46%. CONCLUSION: It is possible to improve the diagnostic accuracy of prostate cancer screening using the cut-off value of PSAV and average PSAV in subjects with initial PSA levels of 1.0-4.0 ng/mL. The cut-off values of PSAV should be set at 1.2 and 0.75 ng/mL per year in individuals with initial PSA levels of 1.0-1.9 and 2.0-4.0 ng/mL, respectively. The cut-off values of the average PSAV should be set at 0.75 and 0.4 ng/mL per year in individuals with initial PSA levels of 1.0-1.9 and 2.0-4.0 ng/mL, respectively.
Adult↗
Salvage external beam radiotherapy for local recurrence without systemic progression or prostate specific antigen recurrence of prostate cancer after initial hormonal therapy: is it possible to identify patients likely to have good treatment outcomes?
BACKGROUND: We attempted to identify factors that predict the outcomes of salvage external beam radiotherapy (sEBRT) in patients who showed local recurrence without systemic progression or isolated prostate specific antigen (PSA) recurrence after initial hormonal therapy. METHODS: The subjects were 33 patients who were diagnosed as having local recurrence without systemic progression (30 cases) or isolated PSA recurrence (three cases). Of these patients, those with continuously decreasing PSA levels, which were 1.0 ng/ml or less 1-1.5 years after sEBRT, were regarded as good responders (GR) whereas the remaining patients were regarded as poor responders (nGR). Survival rates in these patients and factors that distinguish GR from nGR were evaluated retrospectively. RESULTS: The cancer-specific 10-year survival rate was 82.4% in the 33 patients, 100% in the 21 GR patients and 55% in the 12 nGR patients (P < 0.0001). Stepwise variable selection to discriminate between GR and nGR revealed that the time from sEBRT initiation to the nadir PSA was the most significant factor (P = 0.000097). Before sEBRT, GR can be predicted in patients with pre-sEBRT PSA <30.0 ng/ml and PSA doubling time (PSADT) >7.0 months, with a sensitivity of 95.2% (20/21), a specificity of 100% and an accuracy of 97.0%. CONCLUSION: Good responses to sEBRT can be expected in patients with local recurrence without systemic progression or isolated PSA recurrence after initial hormonal therapy when the patients show both pre-sEBRT PSA <30.0 ng/ml and PSADT >7.0 months.
Aged↗
Rapidly progressive malignant epithelioid angiomyolipoma of the kidney.
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Angiomyolipoma↗