The treatment of benign prostatic hyperplasia with 5 mg of finasteride per day results in a significant decrease in symptoms of obstruction, an increase in urinary flow, and a decrease in prostatic volume, but at a slightly increased risk of sexual dysfunction.
The efficacy and tolerance of the nonsteroidal antiandrogen nilutamide in the treatment of prostatic cancer were studied in a large double-blind clinical trial initiated in 1986. Patients with metastatic prostatic cancer without prior endocrine manipulation underwent orchiectomy and were randomized to 1 of 2 groups receiving nilutamide (225 patients) or placebo (232). Nilutamide and placebo were evaluated for efficacy in 207 and 216 patients, respectively. Progression-free survival was significantly longer in the nilutamide group (median time to progression 20.8 months on nilutamide and 14.9 months on placebo, p = 0.005). Median time to death from prostatic cancer was 30.0 months in the placebo group and 37 months in the nilutamide group. Objective regressions were higher in the nilutamide group (41%) than in the placebo group (24%). Significant differences in favor of the nilutamide group were found at several intervals for bone pain, prostatic acid phosphatase, prostate specific antigen, alkaline phosphatase and bone scan isotope uptake. Nilutamide and orchiectomy constitute a more effective treatment for metastatic prostatic cancer than orchiectomy alone, and the adverse effects of nilutamide, usually minor, are outweighed by the significant improvements in most disease measures and progression-free survival.
Human exposure to bisphenol A (BPA) is ubiquitous. Animal studies found that BPA contributes to development of prostate cancer, but human data are scarce. Our study examined the association between urinary BPA levels and Prostate cancer and assessed the effects of BPA on induction of centrosome abnormalities as an underlying mechanism promoting prostate carcinogenesis. The study, involving 60 urology patients, found higher levels of urinary BPA (creatinine-adjusted) in Prostate cancer patients (5.74 µg/g [95% CI; 2.63, 12.51]) than in non-Prostate cancer patients (1.43 µg/g [95% CI; 0.70, 2.88]) (p = 0.012). The difference was even more significant in patients <65 years old. A trend toward a negative association between urinary BPA and serum PSA was observed in Prostate cancer patients but not in non-Prostate cancer patients. In vitro studies examined centrosomal abnormalities, microtubule nucleation, and anchorage-independent growth in four Prostate cancer cell lines (LNCaP, C4-2, 22Rv1, PC-3) and two immortalized normal prostate epithelial cell lines (NPrEC and RWPE-1). Exposure to low doses (0.01–100 nM) of BPA increased the percentage of cells with centrosome amplification two- to eight-fold. Dose responses either peaked or reached the plateaus with 0.1 nM BPA exposure. This low dose also promoted microtubule nucleation and regrowth at centrosomes in RWPE-1 and enhanced anchorage-independent growth in C4-2. These findings suggest that urinary BPA level is an independent prognostic marker in Prostate cancer and that BPA exposure may lower serum PSA levels in Prostate cancer patients. Moreover, disruption of the centrosome duplication cycle by low-dose BPA may contribute to neoplastic transformation of the prostate.
Purpose
Most men with elevated serum prostate-specific antigen (PSA) levels and negative biopsies require repeat biopsy because of the lack of a sensitive and specific prostate cancer (CaP) detection test. This study evaluated the diagnostic potential of a duplex assay for CaP by quantifying transcript levels of α-methylacyl-CoA racemase (AMACR) and prostate-cancer antigen 3 (PCA3) in urine sediments following prostatic message.
Materials and Methods
Urine sediments from 92 patients, 43 with 49 without CaP were collected after digital rectal examination. Transcript levels of AMACR, PCA3, and PSA in total RNA isolated from these samples were determined by absolute qRT-PCR. AMACR and PCA3 scores were obtained by normalizing the transcript level to that of PSA for each sample and multiplying by 100.
Results
AMACR (p=0.006) and PCA3 (p=0.014) scores, but not serum PSA (p=0.306), discriminated specimens from patients with and without CaP, Receiver-operating-characteristic analysis established the diagnostic cutoff scores for the AMACR and PCA3 tests at 10.7 and 19.9, respectively. As determined from these cutoff scores, the AMACR test has 70% (95% CI, 56-83%) sensitivity and 71% (95% CI, 59-84%) specificity, whereas the PCA3 test has 72% (95% CI, 59-85%) sensitivity and 59% (95% CI, 45-73%) specificity for CaP detection. The combined use of AMACR and PCA3 scores in a dual-marker test increased sensitivity to 81% (95% CI, 70-93%) and specificity to 84% (95% CI, 73-94%).
Conclusions
Urinary AMACR and PCA3 tests were both superior to serum PSA test for detecting CaP. Their combined use in a dual-marker test further improved sensitivity and accuracy and could be used as a surveillance test after repeat negative prostate biopsies.
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