Normal PSA After Radical Prostatectomy
PSA should become undetectable (less than 0.1 ng/mL) within the first month after radical prostatectomy, and any PSA value ≥0.2 ng/mL confirmed on two consecutive measurements indicates biochemical recurrence requiring further evaluation. 1, 2
Expected PSA Values Post-Prostatectomy
- Undetectable PSA is defined as <0.1 ng/mL using standard assays or <0.07 ng/mL using ultrasensitive assays 3, 4
- PSA should drop to undetectable levels within 2 months after surgery, given PSA's half-life of approximately 3.5 days 2
- Some assays use a threshold of <0.2 ng/mL, but the more stringent <0.1 ng/mL cutoff is preferred for defining truly undetectable levels 1, 3
Definition of Biochemical Recurrence
The AUA defines biochemical recurrence as an initial PSA value ≥0.2 ng/mL followed by a subsequent confirmatory PSA value ≥0.2 ng/mL. 1 This is the most widely accepted definition, used in 35 of 145 studies reviewed 1.
- A cutpoint of 0.4 ng/mL followed by another increase may better predict metastatic relapse risk, though 0.2 ng/mL remains the standard for reporting outcomes 1
- The 0.2 ng/mL threshold represents a balance between early detection and avoiding false positives from benign tissue remnants 1
Clinical Management Algorithm
If PSA is Detectable at First Post-Operative Test (3-12 months):
- Repeat PSA at 8 weeks to determine if the level is declining toward undetectable 2
- If PSA continues to decline and becomes undetectable, resume standard surveillance 2
- If PSA remains detectable or rises, this indicates biochemical persistence requiring specialist referral 2
If PSA Becomes Detectable After Initial Undetectable Period:
- Confirm with repeat measurement showing PSA ≥0.2 ng/mL on two consecutive tests 1, 2
- Calculate PSA doubling time (PSADT) to assess aggressiveness 1, 3
- Consider salvage radiotherapy, as outcomes are superior when initiated at lower PSA levels 2, 5
Surveillance Protocol for Undetectable PSA
- PSA testing every 6-12 months for the first 5 years, then annually thereafter 2
- Use the same laboratory assay for longitudinal monitoring, as variability can range 20-25% 2
- No imaging is necessary before biochemical recurrence unless complications are suspected 1
Important Caveats
- Benign periurethral glands can secrete small amounts of PSA even after complete prostate removal, but this should remain <0.1 ng/mL 6, 4
- Laboratory variability means a single borderline value (0.1-0.2 ng/mL) requires confirmation before declaring recurrence 2
- Persistent PSA ≥0.1 ng/mL at 3-4 months post-surgery predicts higher clinical progression rates (20% vs 7% at 3 years) compared to undetectable levels 7
- Patients with seminal vesicle invasion or nadir PSA ≥1.0 ng/mL have significantly higher risk of developing castration-resistant disease 5
Salvage Therapy Considerations
- Salvage radiotherapy should be offered to patients with PSA recurrence when there is no evidence of distant metastatic disease 1, 2
- Radiotherapy outcomes are better when PSA is <2.0 ng/mL at time of treatment 1
- Bone scans have <5% yield unless PSA exceeds 40-45 ng/mL in patients not on androgen deprivation 1
- PSADT <10 months, Gleason score 8-10, and pre-radiotherapy PSA >2 ng/mL predict worse outcomes with salvage therapy 1