Varying entry criteria for active surveillance show different rates of adverse pathological features at radical prostatectomy. Predictably fewer men met the more stringent criteria but these men had a lower incidence of seminal vesicle involvement and extracapsular extension. Such data can be used to advise men of the risks of active surveillance.
Intermittent androgen deprivation was not inferior to continuous therapy with respect to the overall survival. Some quality-of-life criteria seemed improved with intermittent therapy. Intermittent androgen deprivation can be considered as an alternative option in patients with recurrent or metastatic prostate cancer.
Purpose: Radical prostatectomy (RP) patients with positive surgical margins are at increased risk for recurrence, emphasizing the need for prognostic markers to stratify probable outcome for optimal patient management decisions. We tested the hypothesis that nuclear localization of nuclear factor (NF)-B, a transcription factor involved in the regulation of cell growth, angiogenesis, invasion, and apoptosis, is associated with an increased risk of biochemical recurrence after RP.Experimental Design: Analyses addressed data from 42 patients (age range, 52-72 years; mean age, 63.7 years) who exhibited positive surgical margins after RP. Immunohistochemical analysis of NF-B (p65) was performed on the positive margin tissue. A nuclear staining cutoff of >5% was considered positive. The relation between nuclear NF-B expression and biochemical recurrence (prostate-specific antigen >0.3 ng/mL and rising) after RP was tested in univariate and multivariate Cox regression models.Results: Biochemical recurrence was recorded in 23 patients (54.8%; median follow-up, 3.2 years). Univariate Cox regression demonstrated a 4.9-fold (95% confidence interval, 1.5-16.7; P ؍ 0.01) higher rate of recurrence in men with NF-B > 5%. In the multivariate model, after controlling for primary (P ؍ 0.004) and secondary (P ؍ 0.7) Gleason patterns, lymph node (P ؍ 0.06) and seminal vesicle invasion (P ؍ 0.2), and preoperative prostate-specific antigen (P ؍ 0.009), NF-B > 5% was associated with a 6.2-fold higher risk of biochemical recurrence (95% confidence interval, 1.7-23.5; P ؍ 0.007).Conclusions: In univariate and multivariate analysis, NF-B nuclear expression was strongly predictive of biochemical recurrence in patients with positive surgical margins after RP. We propose that nuclear NF-B may serve as a useful independent molecular marker for stratifying patients at risk for recurrence.
Purpose: Dietary intake of long-chain N-3 (LC n-3) polyunsaturated fatty acids may reduce inflammation and in turn decrease risk of prostate cancer development and progression. This potential effect may be modified by genetic variation in cyclooxygenase-2 (COX-2), a key enzyme in fatty acid metabolism and inflammation. Experimental Design: We used a case-control study of 466 men diagnosed with aggressive prostate cancer and 478 age-and ethnicity-matched controls. Diet was assessed with a semiquantitative food frequency questionnaire, and nine COX-2 tag single nucleotide polymorphisms (SNP) were genotyped. We used logistic regression models to estimate odds ratios (OR) for association and interaction. Results: Increasing intake of LC n-3 was strongly associated with a decreased risk of aggressive prostate cancer (P trend V 0.0001). The OR (95 % confidence interval) for prostate cancer comparing the highest with the lowest quartile of n-3 intake was of 0.37 (0.25-0.54). The LC n-3 association was modified by SNP rs4648310 (+8897 A/G), flanking the 3 ¶ region of COX-2 (P interaction = 0.02). In particular, the inverse association was even stronger among men with this variant SNP. This reflected the observation that men with low LC n-3 intake and the variant rs4648310 SNP had an increased risk of disease (OR, 5.49; 95% confidence interval, 1.80-16.7), which was reversed by increasing intake of LC n-3. Conclusions: Dietary LC n-3 polyunsaturated fatty acids appear protective for aggressive prostate cancer, and this effect is modified by the COX-2 SNP rs4648310. Our findings support the hypothesis that LC n-3 may impact prostate inflammation and carcinogenesis through the COX-2 enzymatic pathway.
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