To provide insights into the likelihood that benign prostatic tissue represents a source of measurable prostate-specific antigen (PSA) after radical prostatectomy.

From October 2000 to December 2006, 1308 consecutive men underwent open radical retropubic prostatectomy by a single surgeon. Of these 1308 men, 331 (25.3%) met our criteria for having “extremely” low-risk disease as determined by the preoperative and pathologic factors, including a preoperative PSA level <10 ng/mL, clinical Stage T1c or T2a, a Gleason score of ≤6, an estimated cancer volume in the specimen of <5%, and no evidence of positive surgical margins. This cohort was selected because any measurable PSA level would be highly suspicious for a benign origin. Undetectable PSA was defined as a PSA level of ≤0.04 ng/mL. A measurable PSA level included values between 0.05 and 0.14 ng/mL on ≥2 consecutive measurements 6 months apart. Biochemical recurrence was defined as 3 consecutively increasing PSA levels with a peak level of ≥0.15 ng/mL.

At 3 months to 6 years of follow-up (mean 36.2 months), 0.6% and 0.3% of patients had developed a measurable PSA level or biochemical recurrence, respectively. The single patient with biochemical recurrence responded to salvage radiotherapy, strongly suggesting a malignant etiology for the recurrence.

A measurable PSA level or biochemical recurrence was an extraordinarily rare event in our select group of patients with extremely low-risk disease. These results provide compelling evidence that retained benign prostatic elements are an unlikely source of elevated PSA levels in men who have undergone radical prostatectomy.