Prostate biopsy tumor extent but not location predicts recurrence after radical prostatectomy: results from CaPSURE.

PURPOSE: Prostate cancer biopsy information is important for patient risk assessment. Although the number and extent of positive biopsies have been used to predict recurrence, the impact of positive biopsy location and contiguity is less clear. We compared the ability of positive prostate biopsy location and pattern with number and percent positive biopsies to predict recurrence after RP. MATERIALS AND METHODS: From CaPSURE we identified 2,037 men treated with RP from 1992 to 2002 for whom detailed biopsy information and 2 or more followup PSA values were available. Treatment failure was defined as 2 consecutive PSA values of 0.2 ng/ml or higher, or a second treatment delivered more than 6 months after RP. Biopsy tumor volume (number and percent positive sites), location of disease (anatomical site, laterality), and contiguity of positive biopsies were entered into Cox proportional hazards models to predict risk of disease recurrence while controlling for Gleason grade, PSA and T stage. RESULTS: Higher number and percent of positive biopsy cores were associated with prostate cancer recurrence, risk stratification category and Gleason grade, p <0.0001, HR 1.09 (CI 1.02 to 1.16) and 1.01 (CI 1.00 to 1.01), respectively. Number of biopsy cores taken, laterality, contiguity and positive biopsy location were not associated with disease recurrence. CONCLUSIONS: The number and the percentage of biopsies positive for cancer correlated with treatment failure after radical prostatectomy. Contiguity, laterality and location were not associated with recurrence.

Extra-cellular superoxide promotes T cell expansion through inactivation of nitric oxide.

The mechanism and regulation of immunosuppression by nitric oxide (NO) is unclear. Extra-cellular superoxide (EC-O2-) production by NADPH-oxidase (phox) may prevent NO-mediated suppression of T cell proliferation. p47(phox-/-) mice are resistant to experimental allergic encephalomyelitis (EAE), coinciding with enhanced splenic NO activity, but no causal link was established. Here, we demonstrate such link, since p47(phox-/-) mice developed severe EAE by adoptive transfer, but only if NO production during ex vivo donor cell reactivation was inhibited. EC-O2- production increased during cognate T cell reactivation, while inhibition of EC-O2- by exogenous superoxide dismutase enhanced NO activity. By inhibiting NO, EC-O2- production promotes T cell expansion during peripheral immune-response activation, not during tissue inflammation.