Clinical prostate cancer最新文献

Combination therapy consists of castration plus an antiandrogen. Following medical or surgical castration, the androgen receptor can be activated by adrenal androgens, low levels of residual testosterone, and ligand-independent activators. The survival benefit of combination therapy compared with castration alone is one of the most studied questions in urology. Results from trials comparing combination therapy to castration alone are variable. A metaanalysis of 26 randomized trials indicated that the type of antiandrogen used is relevant. Combination therapy using nonsteroidal antiandrogens was associated with a statistically significant overall survival benefit. In contrast, combination therapy using steroidal antiandrogens was associated with reduced survival compared with castration alone. Bicalutamide 50 mg has a number of advantages compared with nilutamide and flutamide when used in combination with castration. These include an improved side-effect profile, once-daily dosing, more potent inhibition of androgen-independent activation of the androgen receptor through favorable interactions with nuclear coactivators and corepressors, and evidence for improved survival in one randomized trial. An analysis combining historic trial data suggests that bicalutamide 50 mg in addition to androgen deprivation may reduce the hazard ratio (HR) for prostate cancer mortality by 20% (HR, 0.80; 95% CI, 0.66-0.98).

The purpose of the study was to determine whether 3D proton magnetic resonance spectroscopic imaging (MRSI) can predict treatment outcome in high risk patients with prostate cancer. Endorectal magnetic resonance imaging (MRI) and ¹H-MRSI were performed in 16 patients with prostate cancer who were considered high risk because of clinical stage T3-4, Gleason score ≥ 8, and/or prostate-specific antigen (PSA) level > 20 ng/mL. Patients were treated with chemotherapy/hormone therapy, underwent radical prostatectomy (RP) or radiation therapy, and were followed for PSA relapse (follow-up, 19-43 months). The ratio of choline plus creatine to citrate was used to localize peripheral zone cancer. An MRSI risk score on a scale of 0-3 was derived from the volume and degree of metabolic abnormality. Magnetic resonance spectroscopic imaging risk score, MRI tumor/node (TN) stage, clinical stage, Gleason score, and PSA were used as predictors of pathologic stage in patients treated with RP (n = 10) and PSA relapse in all patients. Magnetic resonance imaging TN stage (P < 0.01) and MRSI risk score (P < 0.05) correlated with pathologic stage, but clinical stage did not (P = 0.35). Magnetic resonance imaging TN stage was the only significant predictor of PSA relapse in the univariate analysis (P < 0.05). Although the MRSI risk score did not reach significance (P = 0.13), 6 patients with a score < 0.9 were relapse-free, whereas 7 of 10 patients with a score > 0.9 relapsed. Magnetic resonance imaging and MRSI risk assessments agreed in 15 of 16 patients. These preliminary results suggest that tumor metabolic assessment may indicate treatment outcome in high-risk patients with prostate cancer. Although MRSI did not provide added prognostic value to MRI in this small number of patients, MRSI might increase the confidence of the clinician in assessing risk on MRI by contributing supporting metabolic data.

Protease-activated receptor (PAR) 1, PAR3, and PAR4 are considered "thrombin receptors" because thrombin specifically cleaves the extracellular N-termini of the receptor to unmask a new amino acid terminus, which in turn acts as a peptide ligand by binding intramolecularly to the body of the receptor. Among those 3 family members, PAR1 is the predominant thrombin receptor. Although the thrombin-mediated regulation of clot formation has been studied extensively over the past decades, the possible role of thrombin in tumor metastasis via PAR1 has only recently received attention and is briefly discussed herein.

Prostate cancer is the most common malignancy among American men and is the second-leading cause of cancer-related mortality. Although radical prostatectomy and radiation therapy offer hope for cure for the majority of men with localized tumors, we continue to lack the tools to definitively determine which cancers need to be treated, which cancers will recur after treatment, and which cancers will behave aggressively when they have metastasized. Recent breakthroughs in molecular biology have led to the identification of a number of potential biomarkers for prostate cancer, many of which have been suggested to have prognostic significance. Eventually, combinations of these markers will hopefully enable us to more rationally facilitate counseling and direct management for men with prostate cancer.

Although prostate-specific antigen (PSA) is a useful screening marker in prostate cancer, it has limited specificity. Previously it was shown that the amount of surface-bound PSA present on circulating macrophages was different between patients with localized prostate cancer and those with metastatic prostate cancer. It was recently demonstrated that intracellular PSA in macrophages can be measured by flow cytometry. In the context of searching for a noninvasive, highly reliable method for prostate cancer diagnosis, we assessed the extent to which extracellular (ie, surface-bound) and intracellular PSA–positive macrophages might differentiate patients with benign versus malignant prostatic disease. In a pilot study, the levels of complexed, surface-bound, and intracellular PSA were measured in 25 patients with elevated serum PSA values and histologically confirmed disease. In this group, no significant differences for serum PSA and complexed PSA levels, respectively, could be detected among patients with benign prostatic hyperplasia, prostatitis, and prostate cancer. Significant differences, however, were detected in intracellular PSA, although not in surface-bound PSA, among the 3 groups of patients. Intracellular PSA was measured prospectively in a second cohort of 189 patients who had a transrectal biopsy because of a serum PSA constellation suspicious for prostate cancer. In the expanded cohort, highly significant differences in intracellular PSA were observed between benign and malignant disease of the prostate, even in patients with serum PSA level < 4 ng/mL. Screening of serum PSA alone or in combination with complexed PSA does not clearly distinguish patients with prostate cancer from those with prostatitis or benign prostatic hyperplasia. Macrophage intracellular PSA might represent a more sensitive method of screening for prostate cancer than extracellular or serum PSA.

Most patients with metastatic prostate cancer will respond initially to ablation of gonadal androgen production. Eventually, all patients will develop progressive disease despite continued androgen suppression, a condition called androgen-independent or hormone-refractory prostate cancer. Hormone-refractory prostate cancer is characterized by virulent biologic and clinical behavior. Recently, docetaxel-based chemotherapy has been shown to improve survival and quality of life in this disease when compared with mitoxantrone-based therapy. However, results remain suboptimal. Recently, there have been remarkable advances in the delineation of the mechanisms of cancer growth, metastasis, and the intricate interactions between tumor cells and the surrounding normal tissues. The accumulated evidence has confirmed the importance of angiogenesis in these processes and validated the theory that inhibition of neovascularization is a promising therapeutic anticancer strategy. Currently, dozens of compounds that interfere with different steps of the angiogenic cascade are in preclinical and clinical development. Some of these agents have exhibited promising antitumor activity in hormonerefractory prostate cancer. This review summarizes the molecular mechanisms implicating angiogenesis in the development and progression of advanced-stage prostate cancer, as well as the drug development efforts that are targeting this process.