Definition of Biochemical Recurrence of Prostate Cancer
Biochemical recurrence after radical prostatectomy is defined as a PSA ≥0.2 ng/mL with a second confirmatory level ≥0.2 ng/mL, while after radiation therapy it is defined as a PSA rise of ≥2 ng/mL above the nadir PSA. 1
After Radical Prostatectomy
The American Urological Association (AUA) Prostate Guidelines Update Panel established the standardized definition for biochemical recurrence following radical prostatectomy 1:
- PSA threshold: Serum PSA of 0.2 ng/mL or greater
- Confirmation required: A second confirmatory PSA level >0.2 ng/mL
- Timing of first PSA: Obtain between 6 weeks and 3 months following surgery
- Date of failure: Determined "at call" when the confirmatory elevated PSA is documented
Key Implementation Points
The rationale for this definition is based on extensive analysis showing that PSA cutpoints between 0.2-0.4 ng/mL most accurately predict clinical failure 1. The AUA panel reviewed 145 articles with 53 different definitions and found PSA >0.2 ng/mL was the most commonly used (35 studies) 1.
Important considerations:
- A 6-week washout period is essential before obtaining the first postoperative PSA to allow adequate clearance 1
- Any detectable PSA should be repeated for confirmation to eliminate laboratory error 1
- Lower PSA thresholds (0.2 ng/mL) increase sensitivity for detecting ultimate disease recurrence, while higher values (0.4 ng/mL) improve specificity 1
Emerging Evidence for Earlier Intervention
Recent research suggests that lower PSA thresholds may identify patients who benefit from earlier salvage therapy. Studies show that 95.9% of patients with PSA 0.1-0.19 ng/mL will progress to PSA ≥0.2 ng/mL, and early salvage radiotherapy at PSA <0.2 ng/mL improves freedom from progression compared to treatment at PSA ≥0.2 ng/mL 2. However, the standardized definition for reporting outcomes remains PSA ≥0.2 ng/mL with confirmation.
After Radiation Therapy
The Phoenix Consensus Conference (RTOG-ASTRO, 2005) established the current standard definition for biochemical failure after radiation therapy 3:
- PSA threshold: A rise by 2 ng/mL or more above the nadir PSA
- Date of failure: Determined "at call" (not backdated)
- Applies to: External beam radiotherapy with or without hormonal therapy
Comparison to Previous ASTRO Definition
The original 1996 ASTRO definition required 3 consecutive PSA rises after nadir, with the date of failure backdated to the midpoint between nadir and the first rise 1. This definition had significant limitations:
- Performed poorly in patients receiving hormonal therapy
- Backdating artificially inflated success rates
- Time intervals between PSA measurements were not specified
- Did not incorporate PSA nadir as a risk factor
The Phoenix definition (PSA nadir + 2 ng/mL) addressed these shortcomings and is now the recommended standard 3.
Clinical Context
After radiation therapy, PSA does not become undetectable because residual functioning prostatic epithelium continues to produce PSA. The nadir may take 2-3 years to reach 1. The Phoenix definition accounts for this biological difference and provides a more accurate predictor of clinical progression.
Critical Pitfalls to Avoid
Do not compare outcomes between surgery and radiation using the same PSA definition - The biological differences in PSA kinetics make direct comparisons inappropriate 1
Ensure adequate follow-up when reporting outcomes - For radiation therapy, control rates should be reported 2 years short of median follow-up to avoid artifacts from insufficient follow-up 3
Recognize that biochemical recurrence is not a perfect surrogate - While PSA elevation universally precedes metastatic progression, it does not perfectly correlate with clinical progression or prostate cancer-specific mortality 4
Consider PSA doubling time and Gleason score - These variables best predict distant metastasis and mortality among patients with biochemical recurrence 4