Objectives: It is unclear why men who undergo radical prostatectomy (RP) and are found to have pathologically organ-confined disease develop prostate-specific antigen (PSA) recurrences. We previously found that patients with less than 45% of cells in the prostate needle biopsy specimen (PNBx) staining positive for the cell cycle regulator p27 had a significantly increased risk of biochemical recurrence after RP. We sought to determine whether p27 staining in the PNBx specimen might serve as a molecular marker for PSA failure in the subset of patients who develop PSA recurrence despite organ-confined disease at RP.
Methods: The PNBx specimens of 161 men treated with RP between 1991 and 2000 were examined for p27 expression using immunohistochemistry. The p27 cutpoint of less than 45% expression was used to define the high and low-risk categories. Patients were separated into two groups for analysis: organ-confined (pT2 and negative surgical margins) and non-organ-confined (pT2 with positive surgical margins, pT3, pT4, or lymph node involvement). The mean and median follow-up for patients with organ-confined and non-organ-confined disease was 47 and 43 months and 42 and 38 months, respectively. Multivariate Cox proportional hazards analysis was used to examine the preoperative clinical variables that were the strongest predictors of biochemical recurrence after RP among each group.
Results: Among organ-confined patients, p27 expression was the only significant independent predictor of the time to biochemical recurrence after RP (hazard ratio 5.15, 95% confidence interval 1.41 to 18.83, P = 0.013). Among patients with non-organ-confined disease, the percentage of biopsy tissue with cancer, biopsy Gleason score, and PSA level were independent predictors of PSA recurrence. p27 expression was not a significant independent predictor of PSA recurrence among men with non-organ-confined disease.
Conclusions: p27 expression in the PNBx was a significant independent predictor of PSA failure for patients with pathologically organ-confined disease, but not for those with non-organ-confined disease. Patients with organ-confined disease but low p27 expression had a greater than fivefold risk of developing PSA recurrence than were men with high p27 expression, suggesting that p27 may be a molecular marker associated with micrometastatic disease at the time of RP.