Effect of dutasteride on the risk of prostate cancer Andriole, Gerald L; Bostwick, David G; Brawley, Otis W ...
New England journal of medicine/The New England journal of medicine,
04/2010, Letnik:
362, Številka:
13
Journal Article
Recenzirano
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We conducted a study to determine whether dutasteride reduces the risk of incident prostate cancer, as detected on biopsy, among men who are at increased risk for the disease.
In this 4-year, ...multicenter, randomized, double-blind, placebo-controlled, parallel-group study, we compared dutasteride, at a dose of 0.5 mg daily, with placebo. Men were eligible for inclusion in the study if they were 50 to 75 years of age, had a prostate-specific antigen (PSA) level of 2.5 to 10.0 ng per milliliter, and had had one negative prostate biopsy (6 to 12 cores) within 6 months before enrollment. Subjects underwent a 10-core transrectal ultrasound-guided biopsy at 2 and 4 years.
Among 6729 men who underwent a biopsy or prostate surgery, cancer was detected in 659 of the 3305 men in the dutasteride group, as compared with 858 of the 3424 men in the placebo group, representing a relative risk reduction with dutasteride of 22.8% (95% confidence interval, 15.2 to 29.8) over the 4-year study period (P<0.001). Overall, in years 1 through 4, among the 6706 men who underwent a needle biopsy, there were 220 tumors with a Gleason score of 7 to 10 among 3299 men in the dutasteride group and 233 among 3407 men in the placebo group (P=0.81). During years 3 and 4, there were 12 tumors with a Gleason score of 8 to 10 in the dutasteride group, as compared with only 1 in the placebo group (P=0.003). Dutasteride therapy, as compared with placebo, resulted in a reduction in the rate of acute urinary retention (1.6% vs. 6.7%, a 77.3% relative reduction). The incidence of adverse events was similar to that in studies of dutasteride therapy for benign prostatic hyperplasia, except that in our study, as compared with previous studies, the relative incidence of the composite category of cardiac failure was higher in the dutasteride group than in the placebo group (0.7% 30 men vs. 0.4% 16 men, P=0.03).
Over the course of the 4-year study period, dutasteride reduced the risk of incident prostate cancer detected on biopsy and improved the outcomes related to benign prostatic hyperplasia. (ClinicalTrials.gov number, NCT00056407.)
Objectives. Prostate-specific membrane antigen (PSMA) is an integral membrane protein highly specific for the prostate. PSMA may be clinically useful for predicting outcome in patients with prostate ...cancer. We compared the expression of PSMA in prostate adenocarcinoma and lymph node metastases in a large series of patients with node-positive cancer.
Methods. We studied 232 patients with node-positive adenocarcinoma who underwent bilateral pelvic lymphadenectomy and radical retropubic prostatectomy at the Mayo Clinic between 1987 and 1992. Immunohistochemistry was performed using monoclonal antibody 7E11-5.3 directed against PSMA. For each case, the percentage of immunoreactive cells in benign prostate tissue, adenocarcinoma, and lymph node metastases was estimated in 10% increments. Intensity was recorded using a scale of 0 to 3 (0 = no staining, 3 = highest).
Results. Cytoplasmic immunoreactivity for PSMA was observed in all cases in benign epithelium and cancer, and most lymph node metastases. The number of cells stained was lowest in benign epithelium; cancer and lymph node metastases were similar (46.2% ± 27.5% versus 79.3% ± 18.5% versus 76.4% ± 26.1%, respectively; all pairs
P < 0.05). Intensity of staining was greatest in primary cancer and lowest in lymph node metastases.
Conclusions. PSMA is expressed in benign prostatic epithelium and primary cancer in all cases and in 98% of cases with lymph node metastases. Expression of PSMA was greatest in primary cancer for both percentage and intensity of immunoreactive cells. PSMA expression allows the identification of benign and malignant prostatic epithelium and may be a potentially valuable marker in the treatment of patients with prostate cancer.
Prostate specific membrane antigen (PSM) is a membrane-bound antigen that is highly specific for benign and malignant prostate epithelial cells. Its expression in high grade prostatic intraepithelial ...neoplasia (PIN) has not been compared with that in prostate carcinoma.
The authors performed an immunohistochemical study of representative sections from 184 radical prostatectomies from previously untreated patients with pathologic stage T2N0M0 adenocarcinoma treated at the Mayo Clinic between 1987 and 1991. Affinity-purified monoclonal antibody 7E11-5.3 directed against PSM was employed at a concentration of 20 microg/mL overnight. For comparison, serial sections in each case were stained with prostate specific antigen (PSA). Staining for all antibodies was performed using the streptavidin-biotin method. For each case, the percentage of immunoreactive cells in benign epithelium, PIN, and adenocarcinoma was estimated in increments of 10%. Cox proportional hazards models were used to identify the risk of carcinoma recurrence according to the number of immunoreactive PIN or cancer cells for PSM and PSA; the date of radical prostatectomy was used as the starting time, and serum PSA (biochemical) failure or clinical failure was the event. PSA biochemical failure was defined as serum PSA > 0.2 ng/mL at least 30 days after surgery.
Intense cytoplasmic immunoreactivity for PSM was observed in the benign and neoplastic epithelial cells in all cases (100% of cases staining). The number of cells staining was lower in benign epithelium and PIN than in adenocarcinoma (69.5+/-17.3% range, 20-90% vs. 77.9+/-13.2% range, 30-100% vs. 80.2+/-13.7% range, 30-100%, respectively). With rare exceptions, basal cells were negative, and there was no immunoreactivity of the prostate stroma, urothelium, or vasculature. Adenocarcinoma gave the most intense and extensive staining, and the highest grades of adenocarcinoma (Gleason primary patterns 4 and 5) showed staining in virtually every cell; there was greater heterogeneity of staining in lower grades of adenocarcinoma. By contrast, PSA immunoreactivity was more intense and extensive in benign epithelium than in PIN and adenocarcinoma. The number of immunoreactive PIN or cancer cells for PSM and PSA was not predictive of PSA biochemical or clinical failure as defined in this study.
PSM was expressed in all cases of prostate adenocarcinoma, with the greatest extent and intensity observed in the highest grades. The expression increased incrementally from benign epithelium to high grade PIN or adenocarcinoma. Conversely, PSA showed the greatest staining in benign epithelium, with decreased expression incrementally from benign epithelium to high grade PIN or adenocarcinoma. Expression of PSM is clinically useful for the identification of prostate epithelium, particularly PIN or adenocarcinoma, and its expression is regulated independent of PSA. The number of PSM immunoreactive cells was not predictive of recurrence, most likely because of the presence of abundant immunoreactivity in most cases, or because of differential expression in primary and metastatic disease.
BACKGROUND: Chromosome 8 alterations, including loss of 8p21-22 and gain of 8q24, are commonly observed in prostate carcinoma. We examined whether these alterations are associated with poor prognosis ...in prostate cancer. METHODS: We used dual-probe fluorescence in situ hybridization and DNA probes for 8p22 (lipoprotein lipase gene), centromere 8 (8cen), and 8q24 (c-myc gene) to determine the corresponding copy numbers in tumor samples from 144 patients with high-grade, advanced (stage III) prostate carcinoma. Cox models were used for multivariate analysis of systemic progression or patient death from prostate cancer. All statistical tests are two-sided. RESULTS: We classified the 8p22, 8cen, and c-myc copy number as normal, loss, and gain. An additional increase (AI) category of c-myc relative to the centromere copy number (i.e., overrepresentation and amplification of c-myc) was also used. Alterations of 8p22 were not statistically significantly associated with either systemic progression or patient death. Alterations of c-myc were associated with both systemic progression (P = .024) and patient death (P = .039); AI of c-myc showed the poorest outcome. We also evaluated the prognostic relevance of the combined 8p22-8cen-c-myc loci anomaly pattern for the following six patterns: normal-normal-normal, loss-any 8cen-normal, loss-gain-gain, gain-gain-gain, non-loss-any 8cen-AI, and loss-any 8cen-AI, where any 8cen is normal, loss, or gain of the chromosome 8 centromere. Patients with the loss-any 8cen-AI pattern had earlier systemic progression (P = .009) and earlier cause-specific death (P = .013) than did patients with other patterns. Multivariate analyses demonstrated that the loss-any 8cen-AI pattern was an independent risk factor for systemic progression (P<.001) and cause-specific death (P = .002). CONCLUSIONS: Genetic alterations of chromosome 8 appear to accumulate in parallel with the progression of prostate carcinomas. AI of the c-myc gene, especially with loss of 8p22, appears to be associated with poor patient prognosis.
Prostatic stromal proliferations: a review Bostwick, David G.; Egevad, Lars
Pathology,
January 2021, 2021-Jan, 2021-01-00, 20210101, 2021, Letnik:
53, Številka:
1
Journal Article
Recenzirano
Prostatic stromal proliferations account for the majority of benign tumour-like lesions in the prostate. The most common is nodular hyperplasia, seen in a majority of elderly men. Diagnostic ...difficulty is encountered with some variants, including stromal hyperplasia with atypia, characterised by degenerative changes of myofibroblasts. In contrast with benign stromal tumours, malignant stromal tumours of the prostate are rare, accounting for less than 0.1% of all prostatic malignancies. The most common are rhabdomyosarcoma (paediatric) and leiomyosarcoma (adults); others include phyllodes tumour and stromal sarcoma. Some authors lump malignant tumours with poor outcome (e.g., phyllodes tumour and stromal sarcoma) with benign stromal tumours (e.g., stromal hyperplasia with atypia, leiomyoma), considering them collectively to be of uncertain malignant potential, but this approach is discouraged. This review presents a contemporary approach to classification and diagnosis of prostatic stromal tumours.
The automated spring-loaded 18-gauge gun recently introduced for prostatic needle biopsy provides less than half the tissue of the traditional 14-gauge biopsy, possibly influencing the accuracy and ...predictive ability of biopsy tumor grade. In order to determine the value of tumor grade in contemporary needle biopsy specimens, we compared grade in 316 biopsies with matched whole-mounted radical retropubic prostatectomy specimens according to Gleason primary pattern, Gleason secondary pattern, Gleason score, percent of Gleason patterns 4 and 5, and nuclear grade. Biopsy grading accuracy was correlated with rates of capsular perforation, seminal vesicle invasion, pelvic lymph node metastasis, serum prostate specific antigen level, prostatic volume, prostatic weight, cancer volume, perineural invasion, DNA ploidy, and pathologic stage. The greatest grading error was encountered with low-grade tumors; there was no correlation of grading error with clinical staging error or other pathologic factors. Significant differences were noted between biopsy and prostatectomy for Gleason primary pattern, secondary pattern, and score. The percent of poorly differentiated carcinoma (Gleason patterns 4 and 5) in biopsies and prostatectomies showed a moderate positive correlation. The results indicate that the accuracy of 18-gauge needle biopsy in predicting tumor grade in the prostatectomy is similar to that reported with 14-gauge biopsies. Based on these findings, we recommend that the Gleason score (sum of primary and secondary patterns) be employed in all needle biopsies, recognizing that the accuracy of grade is decreased in cases with low-grade cancer and small amounts of cancer.
Cyclooxygenase (COX)-inhibiting drugs have antitumor activity in canine and rodent models of urinary bladder cancer. Two isoenzymes of COX have been identified, COX-1 and COX-2. The purpose of this ...study was to characterize COX-1 and COX-2 expression in human invasive transitional cell carcinoma of the urinary bladder by immunohistochemistry and Western blot analysis. COX-2 was not expressed in normal urinary bladder samples but was detected in 25 of 29 (86%) invasive transitional cell carcinomas of the urinary bladder and in 6 of 8 (75%) cases of carcinoma in situ. These results indicate that COX-2 may play a role in bladder cancer in humans and support further study of COX-2 inhibitors as potential antitumor agents in human bladder cancer.
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