Which patients with undetectable PSA levels 5 years after radical prostatectomy are still at risk of recurrence?--implications for a risk-adapted follow-up strategy.

OBJECTIVES: To determine the predictors of late prostate-specific antigen (PSA) failure among men with an undetectable PSA level 5 years after radical prostatectomy (RP). METHODS: A total of 505 men who had undergone RP for prostate cancer from 1985 to 2000 at Brigham and Women's Hospital and who had ≥ 5 years of recurrence-free survival (ie, all PSA levels < 0.2 ng/mL) constituted the study cohort. Cox multivariate regression analysis was used to determine the factors associated with PSA failure after 5 years. Kaplan-Meier analysis was used to estimate the PSA failure-free survival rate. RESULTS: The median follow-up was 10.7 years after RP (interquartile range 7.8-13.3). No patient had PSA failure at year 5, but the PSA failure-free survival rate for this cohort at year 10 was 88% (95% confidence interval 84.4%-91.0%) and, at year 13, was 82% (95% confidence interval 77.0%-86.0%). On multivariable regression analysis, the factors associated with failure after year 5 were Gleason score 7 (adjusted hazard ratio [AHR] 1.88, P = .036), Gleason score 8-10 (AHR 4.81, P ≤ .002), extracapsular extension (AHR 2.37, P = .003), and seminal vesicle invasion (AHR 1.52, P = .062). CONCLUSIONS: Among men with an undetectable PSA level 5 years after RP, Gleason score 7, Gleason score 8-10, extracapsular extension, and seminal vesicle invasion were significant predictors of subsequent late PSA failure. Patients with these factors (particularly Gleason score 8-10 or seminal vesicle invasion) should have continued close monitoring of their PSA level and consideration of early salvage, as appropriate. However, patients with Gleason score 6 disease were very unlikely to develop late recurrence and might be candidates for less-intense follow-up once they have passed the 5-year mark.

Synthesis and characterization of a redox-active ion channel supporting cation flux in lipid bilayers.

The synthesis, cation binding and transmembrane conductive properties of a novel synthetic ion channel containing a redox-active ferrocene unit are described. Fluorescence spectroscopy was used to demonstrate that the channel supports multiple ion coordination and association constants for 1:1 and 1:2 (channel:cation) coordination for both Na(+) and K(+) were evaluated. Experiments using a black lipid membrane preparation revealed that this compound functioned effectively as an ion channel for both Na(+) and K(+). Concomitant (23)Na NMR spectroscopy studies supported this finding and revealed a Na(+) flux, at least 5 times higher than ion transport rates by monensin. Furthermore, oxidation of the redox-active centre (Fe(2+) to Fe(3+)) effectively inhibited ion transport.