How to explore the patient with a rising PSA after radical prostatectomy: defining local versus systemic failure

We report on the various methods used to determine local or distant recurrences in patients with detectable serum prostate-specific antigen (PSA) after radical prostatectomy (RP). Studies show that variables that help predict distant metastases are PSA recurrence less than 2 years following surgery, tumors with Gleason score (GS) greater than 7, and positive seminal vesicles or positive lymph nodes at the time of surgery. In addition, studies in PSA kinetics show that short PSA doubling times, especially less than 6 months, are associated with distant recurrence and better correlated with the pattern and incidence of clinical recurrence than preoperative PSA, specimen GS, or stage alone. Studies show that although positive surgical margins are a significant risk factor for recurrence, only 40% to 50% of patients with positive margins developed an elevated PSA level within 5 years. When suspecting a local recurrence, transrectal ultrasound (TRUS) and TRUS-guided biopsies enhance the relatively inaccurate detection of local recurrence by digital rectal examination and initial prostate fossa biopsies. For distant recurrence, bone scintigrams of patients with a PSA recurrence following RP are only rarely positive and are found to have limited usefulness until the PSA increases to above 30 ng/mL. The role of immunoscintography to differentiate between local and distant recurrence is still evolving and requires further investigation. Further studies are clearly needed to enhance our ability to distinguish local from distant recurrence and to ultimately help guide therapy.