Natural history of disease progression in patients who fail to achieve an undetectable prostate-specific antigen level after undergoing radical prostatectomy

Background: To the authors' knowledge, the natural history of disease progression to distant metastasis is unknown in men who fail to achieve an undetectable prostate-specific antigen (PSA) level after radical retropubic prostatectomy (RRP),. The authors assessed the clinical outcome of men with a persistently detectable PSA level after RRP for clinically localized prostate carcinoma.

Methods: Between 1989 and 2002, 160 men failed to achieve an undetectable PSA level (>/= 0.1 ng/mL) after undergoing RRP for clinically localized prostate carcinoma. No patient received adjuvant therapy before documented metastasis. The Kaplan-Meier method was used to estimate distant metastasis-free survival. Univariate and multivariate Cox proportional hazards regression was used to assess the ability of clinical and pathologic variables to predict distant metastasis-free survival.

Results: The probability of distant metastasis-free survival at 3 years, 5 years, and 10 years was reported to be 68%, 49%, and 22%, respectively. Seventy-five men (47%) developed distant metastases after RRP (median time to metastases of 5.0 years; range, 0.5-13 years). The combination of RRP Gleason score, seminal vesicle status, and lymph node status resulted in 3 risk groups for the prediction of distant metastasis-free survival (hazards ratio [HR] = 1.6; P < 0.01). The slope of PSA changes approximately 3-12 months after RRP at a cutoff value >/= 0.05 was found to be even more predictive of distant metastasis-free survival (HR = 2.9; P < 0.01).

Conclusions: Many patients remained free of metastatic disease for an extended period despite failing to achieve an undetectable PSA level after undergoing RRP for clinically localized prostate carcinoma. However, other patients experienced rapid disease progression to distant metastasis. The authors defined clinical (PSA slope) and pathologic (Gleason score) prognostic variables to help identify those patients with a higher risk of developing distant metastasis after undergoing RRP.