Correlation of pathologic findings with progression after radical retropubic prostatectomy

BACKGROUND: This study was performed to evaluate the effect of positive margins, Gleason grade, and capsular penetration on progression after radical prostatectomy. METHODS: The authors followed 507 men with totally embedded retropubic prostatectomy specimens performed for clinical Stages A and B prostate cancer for a mean of 3.9 years. RESULTS: Fifty-nine percent of the specimens had negative margins, 37% had focally positive margins, and 4% had extensive positive margins. Although some positive margins were the result of extensive and/or high-grade tumor, in many cases, the tumors only focally reached the capsular margin such that positive margins resulted from an inability to remove additional soft tissue surrounding the prostate. Gleason sum 7 tumors had a significantly higher progression rate compared with Gleason sum 5 or 6 ones, although historically Gleason sum 5-7 lesions had been considered together as intermediate-grade tumors. In a multivariate analysis, positive margins and Gleason sum strongly correlated with progression, whereas capsular penetration did not. Only approximately 50% of patients with positive margins experienced disease progression during 5 years of follow-up. The most common single sites of positive margins were distal (22%), posterior (17%), and posterolateral (14%); 22% of positive margins were extensive. Only four patients (0.8% of the total) had positive margins only in the region of the spared neurovascular bundle and experienced progression. CONCLUSIONS: The most likely explanation for the discrepancy between margins and progression is that some of these margins represented artifactually positive margins caused by the unique problems with handling and assessing radical prostatectomy specimens. Radical prostatectomy provided excellent local control, with only 8% of patients exhibiting local recurrence. Sixty-one percent of men with progression had an elevated serum prostate-specific antigen level as their only manifestation of progression. The significance of isolated elevated serum prostate-specific antigen levels is uncertain, and long-term morbidity and mortality will depend on whether these patients have local disease or occult distant metastases.